HCC Cases Research Articles

Serum Biomarkers Study and the Establishment of Diagnostic Models for Hepatitids B-Related HCC

China's HCC accounts for 90% of HBV related HCC. Early detection, diagnosis and treatment are the key to effective control of HCC. By measuring the levels of expression of AFP, DCP and GP73 in the serum of HBV-related HCC patients, the diagnostic value of single and combined detection of the above indicators in HBV-related HCC shall be discussed, and the mathematical model of differential diagnosis by SVM shall be established to provide reference for the diagnosis of HBV-related HCC. A total of 301 patients and healthy persons from March 2016 to January 2018 from Beijing Tongren Hospital affiliated to Capital Medical University have been selected. These lection includes 57 cases of HBV-related HCC, 61 cases of non- HBV-related HCC, 52 cases of HBV-related cirrhosis, 57 cases of chronic HBV, and 74 healthy persons in the same period. The levels of serum DCP, AFP and GP73 in each group were measured. Combined diagnosis of three indexes is better than single diagnosis, P<0.001. Using SVM mathematical diagnosis model, the specificity and sensitivity of diagnosing HBV-related HCC and healthy controls reached 98.7% and 97.6%, while the specificity and sensitivity of diagnosing HBV-related HCC and HBV-related cirrhosis reached 90.91% and 96.3%, respectively. Serum DCP, AFP and GP73 can be used independently as a useful reference for diagnosing HBV-related HCC patients. Combined detection of the three indicators can improve the sensitivity of HBV-related HCC diagnostic test. The SVM model can be used to diagnose and identify liver diseases at different stages.

Significance of Toll-like Receptor 4 ( TLR4 )& Liver Fatty Acid-binding Protein (L-FABP) Expression in Hepatocellular Carcinoma An Immunohistochemical Study

Back ground: Persistent inflammatory conditions can induce tumorigenesis . It is therefore very important to explore the molecular mechanisms involved in progression from chronic hepatitis to cirrhosis to HCC - to identify factors useful for the development of effective therapies that improve patient survival. Aim of the study: Evaluation of TLR-4 and L-FABP expression in cases of chronic hepatitis, cirrhosis and HCC and correlate them with clinicopathological parameters. Methods: A retrospective, immunohistochemical study was performed on 50 liver cases; 32 cases of HCC, 10 cases of chronic hepatitis C, and 8 cases of cirrhosis. Results: There was statistical significant increase in TLR-4 expression in HCC than both chronic liver hepatitis and cirrhosis (P<0.05). There was positive statistical significant correlation between TLR-4expression and size & grade of HCC (P<0.05) . There was highly statistical significant decrease in L-FABP expression in HCC than both chronic liver hepatitis and cirrhosis (P< 0.001). Conclusion: TLR-4 has a role in hepatocarcinogenesis as TLR-4 expression increased with progression from chronic hepatitis to cirrhosis to HCC. Increased TLR-4 expression associated with large tumor size and higher grade of HCC, so it may serve a tool for prognosis of HCC. L-FABP expression decreased with progression from chronic hepatitis to cirrhosis to HCC. So its downregulation may contribute in pathogenesis of HCC.

LncRNA NBR2 inhibits tumorigenesis by regulating autophagy in hepatocellular carcinoma

Long noncoding RNAs (lncRNAs) have been identified to play increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. LncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is demonstrated to decrease in several cancers. However, it is still unknown whether lncRNA NBR2 is involved in hepatocellular carcinoma and autophagy. We found that HCC cases with lower NBR2 expression had significantly worse overall survival than those with higher NBR2 expression in advanced patients. And the expression of NBR2 was negatively correlated with the degree of malignancy of HCC cell lines and differentiation of hepatocellular carcinoma. Besides, NBR2 inhibited the proliferation, invasion, and migration of liver cancer cells. We further found that NBR2 repressed cytoprotective autophagy to restrain HCC cell proliferation. Moreover, NBR2 inhibited Beclin 1-dependent autophagy through ERK and JNK pathways. Taken together, NBR2 suppressed autophagy-induced cell proliferation at least partly through ERK and JNK pathways. These data indicated that NBR2 served as a tumor suppressor gene in hepatocellular carcinoma. The current study provides a novel insight and treatment strategy for hepatocellular carcinoma.

Molecular subtypes based on immune-related genes predict the prognosis for hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is a malignancy exhibiting the highest lethality. The present study aimed to identify different immune-related clusters in HCC and a robust tumor gene signature to facilitate the prognosis prediction for HCC patients. MethodsFor the 375 HCC cases collected from the dataset of Cancer Genome Atlas (TCGA), their overall survival (OS) and immune‐related genes (IRGs) expression patterns were collected. Thereafter, consensus clustering was employed for grouping and functional enrichment, whereas the ESTIMATE algorithm and the CIBERSORT algorithm were used in subsequent assessment. Immunohistochemistry (IHC) was conducted to verify the protein expression of model genes in HCC and adjacent tissues. ResultsAccording to consensus clustering with 93-survival related IRGs, a total of five subgroups were found. These five clusters had different prognoses, immune statuses, and expression of immune checkpoints. Afterwards, 11 genes were enrolled for constructing the OS-related prediction model for TCGA HCC cases, which was then validated using the database of International Cancer Genome Consortium (ICGC). The protein expression of LCN2, S100A10, FABP6, PLXNA1, KITLG and OXTR were enhanced in HCC tissues relative to that in normal hepatic tissues, while the protein expression of S100A1, CCL26, CMTM4, IL1RN and RARG were reduced in HCC compared with normal tissues. In addition, different immunocyte infiltration levels between low- and high- groups were further examined. ConclusionsAccording to our results, the IRGs-based classifications assist in explaining the HCC heterogeneity, which may help to develop the more efficient individualized treatments.

The case for simplifying and using absolute targets for viral hepatitis elimination goals.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries' progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

Abstract 4647: Diet quality indexes and risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study

Abstract Background. There is a limited research on the association between combined dietary measures and liver cancer risk. We investigated the association between the four diet-quality index (DQI) scores, the Alternative Health Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED); Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI) with liver cancer risk, using data from the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45-74 at enrollment in 1993-1998 with up to 25 years of follow-up. Methods. The Cox proportional hazard regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of HCC with each DQI after adjustment for multiple potential confounders. The unconditional logistic regression method was used to evaluate the associations between the DQIs and HCC risk among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg). Results. During an average 17.7 years of follow-up, 561 incident HCC cases were identified. High scores of AHEI-2010, aMED and DASH, representing higher dietary quality, were associated with lower risk of HCC (all Ptrend&amp;lt;0.05). Compared with the lowest quartile, HRs (95% CIs) of HCC risk for the highest quartile of AHEI-2010, aMED and DASH were 0.71 (0.55-0.91), 0.73 (0.54-0.98), and 0.68 (0.52-0.89), respectively. These inverse associations were stronger in men than in women. No significant association between HDI and HCC risk was observed. Among HBsAg-negative individuals, similar inverse associations were observed, and the strongest inverse association was for aMED that reached statistically significance level (HRQ4vsQ1=0.48, 95% CI: 0.24-0.98). Conclusion. Higher scores of AHED, aMED, and DASH were significantly associated with reduced risk of HCC in this Asian population. The findings support the notion that adherence to a healthier diet may lower the risk of HCC, suggesting that dietary modification may be an effective approach for primary prevention of HCC. Funding: The Singapore Chinese Health Study was supported by the National Institutes of Health (NIH) of the United States (grants # R01 CA144034 and UM1 CA182876). Citation Format: Hung N. Luu, Nithya Neelakantan, Ting-ting Geng, Renwei Wang, Jennifer Adams-Haduch, Aizhen Jin, Rob M. Van Dam, Woon-Puay Koh, Jian-Min Yuan. Diet quality indexes and risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4647.

Single center analysis of therapy and outcomes of hepatocellular carcinoma in Sub-Saharan Africa

ABSTRACT Purpose To evaluate the characteristics and response to therapy for HCC in sub-Saharan Africa. Patients and methods We retrospectively evaluated demographic, clinical and outcome variables of HCC in a referral clinic in Ethiopia from 2016 to 2018. Survival assessment was performed using the Mann-Whitney test. Associations between categorical variables was assessed using Pearson Chi-square test. Results We report 46 HCC cases with a median age of 54 years (IQR 45–62) and 50% female. Viral hepatitis was the most common underlying etiology, with 41% of subjects infected with hepatitis B virus (HBV) and 45% with hepatitis C. The median MELD was 12 (IQR 8–17), we found no association between survival and a MELD score </> 15, regardless of underlying disease (pr=0.61, p>0.05). 31% of individuals underwent supportive treatment with a median survival of 27 days (IQR 19–181), 18% used Sorafenib (median survival of 94 days, IQR 24–121), and trans-arterial chemoembolization (TACE) was utilized in 16% (median survival of 352 days, IQR 30–436). HBV cases were diagnosed younger (31% before the age of 40) and those on Tenofovir had a longer median survival than those off Tenofovir (121 vs 34 days). Conclusion Our study found that antiviral treatment of HBV infection was associated with longer survival in HCC. Furthermore, Sorafenib seemed beneficial in patients that used this modality and NLR was a good prognostic factor.

Heat shock protein-27 and MiR-17-5p are novel diagnostic and prognostic biomarkers for hepatocellular carcinoma in Egyptian patients

BackgroundHepatocellular carcinoma (HCC) represents the fourth common cause of cancer related death worldwide. HCC prognosis is still miserable due to its late diagnosis and limited treatment strategies, especially in cases with underlying chronic liver diseases as liver cirrhosis (LC). ObjectiveTo check the utility of Hsp27and miR-17-5p expression as early non-invasive diagnostic biomarkers for HCC on top of liver cirrhosis and their association with clinico-pathological parameters. Design and methodsThis case control study included 95 HCC cases and 103 LC patients without HCC. Liver cirrhosis was diagnosed by abdominal ultrasound during clinical examination, liver function tests and liver biopsy. HCC was diagnosed by ultrasound and/or CT or MRI, Alpha Fetoprotein (AFP) and histopathology. Total RNA was extracted from cancerous tissue and surrounding tissues in HCC patients and from blood and serum of both groups. Expression of blood Hsp27 and serum MiR-17-5p were studied by quantitative real time PCR (qRT-PCR). ResultsHsp27 and miR-17-5p mRNA expression were significantly augmented in HCC patients in comparison to LC patients and in malignant tissues as compared to non-malignant adjacent tissues in HCC patients. In blood of HCC patients, Hsp27 mRNA expression was significantly elevated and correlated with big tumour size, number of tumour lesions, high histopathological grades, metastasis and HBV or HCV infection. Serum miR-17-5p mRNA level was significantly enhanced and associated with number of tumour lesions, vascular invasion, stage and metastasis. ConclusionHsp27 and miR17-5p expression levels are augmented in HCC patients and associated with some clinicopathological criteria. Therefore, they can be used as novel non-invasive biomarkers for HCC diagnosis and prognosis in Egyptian patients.

Identification of a protein signature for predicting overall survival of hepatocellular carcinoma: a study based on data mining

BackgroundHepatocellular carcinoma (HCC), is the fifth most common cancer in the world and the second most common cause of cancer-related deaths. Over 500,000 new HCC cases are diagnosed each year. Combining advanced genomic analysis with proteomic characterization not only has great potential in the discovery of useful biomarkers but also drives the development of new diagnostic methods.MethodsThis study obtained proteomic data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) and validated in The Cancer Proteome Atlas (TCPA) and TCGA dataset to identify HCC biomarkers and the dysfunctional of proteogenomics.ResultsThe CPTAC database contained data for 159 patients diagnosed with Hepatitis-B related HCC and 422 differentially expressed proteins (112 upregulated and 310 downregulated proteins). Restricting our analysis to the intersection in survival-related proteins between CPTAC and TCPA database revealed four coverage survival-related proteins including PCNA, MSH6, CDK1, and ASNS.ConclusionThis study established a novel protein signature for HCC prognosis prediction using data retrieved from online databases. However, the signatures need to be verified using independent cohorts and functional experiments.

Evaluation of Primary Liver Cancers Using Hepatocyte-Specific Contrast-Enhanced MRI: Pitfalls and Potential Tips.

When radiologists interpret hepatic focal lesions seen on dynamic magnetic resonance imaging (MRI) scans, it is important not only to distinguish malignant lesions from benign ones but also to distinguish nonhepatocellular carcinoma (HCC) malignancies from HCCs. In addition, most major guidelines, including those of the American Association for the Study of Liver Disease, European Association for the Study of the Liver, and Korean Liver Cancer Association and National Cancer Center, allow for the noninvasive imaging diagnosis of HCC in at-risk patients. However, ~40% of HCC cases show atypical imaging features mimicking non-HCC malignancies. Furthermore, several benign and malignant lesions, such as flash-filling hemangioma and intrahepatic mass-forming cholangiocarcinoma, frequently look like HCC. In contrast, although multiparametric MRI options, including hepatobiliary phase and diffusion-weighted imaging, provide useful information that could help address these challenges, there remain several unresolved issues with regard to the noninvasive diagnostic criteria characterizing HCC. In this article, we discuss the typical imaging features and challenging situations related to primary liver cancers in MRI, while considering how to make a correct diagnosis. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?

BACKGROUNDHepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) differ in treatment and prognosis, warranting an effective differential diagnosis between them. The LR-M category in the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) was set up for lesions that are malignant but not specific to HCC. However, a substantial number of HCC cases in this category elevated the diagnostic challenge.AIMTo investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS.METHODSPatients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC (HCC classified in the CEUS LI-RADS LR-M category) between January 2015 and October 2018 were included in this retrospective study. Each ICC was assigned a category as per the CEUS LI-RADS. The enhancement pattern, washout timing, and washout degree between the ICC and LR-M HCC were compared using the χ2 test. Logistic regression analysis was used for prediction of ICC. Receiver operating characteristic (ROC) curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC.RESULTSA total of 228 nodules (99 ICCs and 129 LR-M HCCs) in 228 patients were included. The mean sizes of ICC and LR-M HCC were 6.3 ± 2.8 cm and 5.5 ± 3.5 cm, respectively (P = 0.03). Peripheral rim-like arterial phase hyperenhancement (APHE) was detected in 50.5% (50/99) of ICCs vs 16.3% (21/129) of LR-M HCCs (P < 0.001). Early washout was found in 93.4% (93/99) of ICCs vs 96.1% (124/129) of LR-M HCCs (P > 0.05). Marked washout was observed in 23.2% (23/99) of ICCs and 7.8% (10/129) of LR-M HCCs (P = 0.002), while this feature did not show up alone either in ICC or LR-M HCC. Homogeneous hyperenhancement was detected in 15.2% (15/99) of ICCs and 37.2% (48/129) of LR-M HCCs (P < 0.001). The logistic regression showed that rim APHE, carbohydrate antigen 19-9 (CA 19-9), and alpha fetoprotein (AFP) had significant correlations with ICC (r = 1.251, 3.074, and -2.767, respectively; P < 0.01). Rim APHE presented the best enhancement pattern for diagnosing ICC, with an area under the ROC curve (AUC) of 0.70, sensitivity of 70.4%, and specificity of 68.8%. When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP, the AUC and sensitivity improved to 0.82 and 100%, respectively, with specificity decreasing to 63.9%.CONCLUSIONRim APHE is a key predictor for differentiating ICC from LR-M HCC. Rim APHE plus elevated CA 19-9 and normal AFP is a strong predictor of ICC rather than LR-M HCC. Early washout and marked washout have limited value for the differentiation between the two entities.

Hepatitis B virus preS2Δ38-55 variants: A newly identified risk factor for hepatocellular carcinoma.

Background & AimsAlthough HBV is a major cause of death in Africa, its genetic variability has been poorly documented. This study aimed to address whether HBV genotype and surface gene variants are associated with HBV-related liver disease in The Gambia.MethodsWe conducted a case-control study nested in the Prevention of Liver Fibrosis and Cancer in Africa programme. Consecutive treatment-naive patients with chronic HBV infection and detectable viral load were recruited: 211 controls with no significant liver disease and 91 cases (56 cirrhosis and 35 HCC cases). HBV genotypes and surface gene variants were determined by Sanger sequencing or next-generation sequencing (NGS) in serum DNA. Aflatoxin B1 (AFB1)-specific codon 249 TP53 mutation was determined by NGS in circulating cell-free plasma DNA.ResultsIn phylogenetic analysis, 85% of individuals carried HBV genotype E, 14% genotype A, and 1% A/E recombinant viruses. Surface gene variants were more frequently observed in cases (43% and 57% in cirrhosis and HCC cases, respectively) than controls (25%; p <0.001), with preS2 deletions between nucleotides 38–55 (preS2Δ38–55) being the main genetic variant detected. In multivariable analysis, HBeAg seropositivity, low HBsAg levels, and HDV seropositivity were significantly associated with cirrhosis and HCC, whilst older age, higher viral load, genotype A, preS2Δ38–55, and AFB1 exposure were only associated with HCC. There was a multiplicative joint effect of preS2Δ38–55 variants with HBeAg seropositivity (odds ratio [OR] 43.1 [10.4–177.7]), high viral load >2,000 IU/ml (OR 22.7 [8.0–64.9]), HBsAg levels <10,000 IU/ml (OR 19.0 [5.5–65.3]), and AFB1 exposure (OR 29.3 [3.7–230.4]) on HCC risk.ConclusionsThis study identified a hotspot for HBV preS2 deletions as a strong independent factor for HCC in The Gambia, with HBV genotypes and AFB1 exposure contributing to the high liver cancer risk.Lay summaryAlthough HBV-related liver disease is highly prevalent in sub-Saharan Africa, the associated virological characteristics are poorly studied. Using clinical data from African patients chronically infected with HBV, an assessment of the virological variability (genotypes and mutations) and exposure to AFB1, a toxin often contaminating food, was carried out. Our results show that HBV genotypes, the presence of a highly prevalent mutant form of HBV, and AFB1 exposure contribute to the high liver cancer risk in this population.

ЗАСТОСУВАННЯ ПЕРКУТАННОЇ ХІМІЧНОЇ АБЛЯЦІЇ В ЛІКУВАННІ ПАЦІЄНТІВ З ГЕПАТОЦЕЛЮЛЯРНОЮ КАРЦИНОМОЮ

Щороку частота виявлення ГЦК невпинно зростає. У період з 1990 по 2015 рік показник вперше діагностованих випадків ГЦК збільшився на 75%. В Україні за 2018 рік спеці- альним лікуванням охоплено лише 18,0% первинних хворих: тільки хірургічним лікуванням - 4,9%, комбінованим та комплексним лікуванням — 2,0 %. Незадовільні результати з охоплення спеціальним лікування пов'язані з особливостями етіопатогенезу ГЦК, асимптоматичним пе- ребігом та недосконалою системою скринінгу пацієнтів групи ризику, що утруднює діагнос- тику захворювання на ранніх стадіях. Вибір тактики лікування ГЦК асоційованою з вірусним гепатитом і цирозом печінки досі залишається складною клінічною проблемою, оскільки “за- стосування радикального лікування на ранній стадії є наріжним каменем для покращення за- гальної виживаності таких пацієнтів. Пацієнтам з ГЦК на ранніх стадіях з цирозом печінки, що не підлягають радикальному хірургічному лікуванню на момент звернення, показано засто- сування методів перкутанної абляції — радіочастотна абляція, хімічна абляція, кріоабляція, мікрохвильова абляція тощо. Основними показаннями для застосування локальної абляції в лікуванні ГЦК — дуже рання та рання стадія (за BCLC – стадія 0 та А), компенсована або субкомпенсована функція печінки при цирозі (Child - Pugh клас A та B), загальносоматичний статус за ECOG 0–1, діаметр пухлинного вогнища до 5,0 см (найбільш оптимально до 3,0 см), вогнищеве вузлове ураження, солітарне або множинне ураження. Перкутанну абляцію застосо- вують у якості “брідж”-терапії з метою локального контролю пухлинного росту у пацієнтів, що відповідають Міланським критеріям, критеріям UCSFC і знаходяться в списку очікуван- ня на трансплантацію. Також дані методи показали свою ефективність як неоад'ювантна “downstaging”-терапія у хворих, що не відповідають критеріям для трансплантації печінки та/або з первинно нерезектабельним ураженням. Протягом багатьох десятиліть перкутан- на хімічна абляція була “золотим” стандартом мініінвазивного лікування ГЦК. Даний метод простий у виконанні, не потребує спеціального обладнання, добре переноситься пацієнтами, безпечний та економічно вигідний. Основні хімічні агенти - етанол та оцтова кислота. Про- цедура перкутанної хімічної абляції передбачає інтратуморальне введення хімічного агенту “real-time” під контролем методів візуалізації (УЗД або КТ). Хімічна абляція - це метод дру- гої лінії і застосовується лише у випадках, наявності протипоказань до виконання радіочас- тотної абляції. Даний метод не супроводжується тяжкими специфічними ускладненнями та летальністю. Ефективність її клінічного застосування безпосередньо залежить від розміру пухлинного вогнища. Оптимальний розмір пухлинного вогнища становить не більше 3,0 см. Інтратуморальне введення етанолу призводить до некротизації 90% -100% пухлинних вузлів ГЦК діаметром ≤ 2,0 см та 70% при пухлинах 2,0 - 3,0 см.

The Diagnostic role of Soluble (sAxl) Level in Patients with Hepatocellular Carcinoma compared to Alpha-fetoprotein

Background and Aim: Hepatocellular carcinoma deemed for the plurality of primary liver cancers. Malignancy of the liver is the fourth most popular etiology of cancer mortality worldwide. The high mortality of HCC cases is linked to the delay in diagnosis. Aberrant expression of Axl frequently occurs in many malignancies and is critical for promoting cell proliferation, migration, angiogenesis and metastasis. Axl deregulated activation or expression is linked to resistance to targeted cancer therapies. we aimed to to clear up the diagnostic role of sAXL in HCC patients. Methods: Study included 90 participants; 40 HCC patients on top of liver cirrhosis, 30 patients with liver cirrhosis and twenty healthy subjects (controls). CBC, liver and kidney function tests, alpha-fetoprotein, abdominal ultrasound and triphasic CT were performed. sAxl was assessed by ELISA. Results: sAxl was considerably higher in HCC patients than in cirrhotic and control participants (p 63.5, AFP at cut off >40.34 has sensitivity, specificity and AUC 57.5%, 60% and 0.675 respectively. The combination of AFP and sAxl at related cut off points has higher sensitivity (97.5%) and AUC 0.972 in predicting HCC in cirrhotic patients. sAxl was positively correlated with tumor size. Conclusion: sAxl outperforms AFP in detecting HCC, especially in early HCC and in AFP-negative HCC. Combination of sAxl with AFP improved the sensitivity for early HCC diagnosis.

Hepatocellular carcinoma in Ghana: a retrospective analysis of a tertiary hospital data.

IntroductionHepatocellular carcinoma (HCC) is a cancer of global public health concern because of its high incidence and mortality. The impact is greatest in areas with high prevalence of its major risk factors including chronic hepatitis B virus (HBV). HBV is endemic in Ghana but a comprehensive data on HCC is lacking. The aim of this study was to describe the clinical, laboratory and radiological features of HCC at the Korle Bu Teaching Hospital in Ghana.MethodsThe medical records of 194 HCC cases attended to at the Gastrointestinal Clinic of the Korle Bu Teaching Hospital between January 2015 and December 2018 were retrospectively analyzed for demographic, clinical, laboratory and radiological data.ResultsThe male: female ratio was 2:1 and mean age was 45.2 years. Weight loss and abdominal pain were the major presenting symptoms. No patients were identified through surveillance. HBsAg was positive in 109/145 (75.2%) of cases tested. Sixty-five (59.6%) of 109 HBsAg positives were aware of their HBsAg status but only 3 were receiving medical follow ups prior to the diagnosis of HCC. Raised alpha-fetoprotein level >165.2 IU/ML was found in 53.9%. One hundred and forty-four patients were eligible for only analgesia.ConclusionHBV infection is the leading aetiologial risk factor associated with HCC. Majority of HBV carriers are aware of their status but do not receive care prior to HCC diagnosis. Majority present late and are eligible for only palliative treatment. Improvement in the health seeking behavior of HBV carriers can aid early detection of HCC.

High methylation levels of histone H3 lysine 9 associated with activation of hypoxia-inducible factor 1α (HIF-1α) predict patients’ worse prognosis in human hepatocellular carcinomas

Although it is becoming increasingly apparent that histone methyltransferases and histone demethylases play crucial roles in the cellular response to hypoxia, the impact of hypoxic environments on global patterns of histone methylation is not well demonstrated. In this study, we try to detect the global levels of histone lysine methylation in HCC cases and analyze the correlation between these modifications and the activation of hypoxia-inducible factor 1α (HIF-1α). Immunohistochemistry was used to detect the global levels of histone H3 lysine 9 dimethylation (H3K9me2), histone H3 lysine 9 trimethylation (H3K9me3), histone H3 lysine 27 trimethylation (H3K27me3) and the nuclear expression of HIF-1α in tissue arrays from 111 paraffin-embedded HCC samples. Our analyses revealed that the global levels of H3K9me2, H3K9me3 and the nuclear expression of HIF-1α were distinctly higher in HCC tissues than in peritumoral tissues. Both H3K9me2 and H3K9me3 were positively correlated with the degree of tumor differentiation and the patients’ prognosis. Analysis based on the Pearson's correlation coefficient indicated a positive correlation between H3K9me2 and the nuclear expression of HIF-1α, and meanwhile, a significant correlation between the expression of H3K9me2 and H3K9me3 was also found. In addition, the combination of H3K9me2, H3K9me3 and HIF-1α, rather than one single histone modification or molecular maker, is a better prognostic maker for HCC patients. These findings provide new insights on the complex networks underlying cellular and genomic regulation in response to hypoxia and may provide novel targets for future therapies.

Clinical significance of combined circulating TERT promoter mutations and miR-122 expression for screening HBV-related hepatocellular carcinoma

Telomerase reverse-transcriptase (TERT) gene promoter mutations in circulating cell-free DNA (cfDNA) as well as the levels of circulating microRNA-122 (miR-122) have been reported as potential noninvasive biomarkers for several. This study evaluates the diagnostic performance of potent biomarker-based panels composing of serological AFP, miR-122 and circulating TERT promoter mutations for screening HBV-related HCC. TERT promoter mutations (C228T and C250T) and miR-122 expression were assessed in the plasma samples from 249 patients with HBV-related liver diseases by nested PCR and qRT-PCR assays, respectively. The diagnostic values of TERT promoter mutations, miR-122 expression and biomarker-based panels were assessed by computation of the area under the curve (AUC). Nested-PCR assays were optimized to detect C228T and C250T mutations in TERT promoter with detection limit of 1%. The common hotspot C228T was observed in 22 HCC cases. The triple combinatory panel (AFP@TERT@miR-122) acquired the best diagnostic value to distinguish HCC from CHB (AUC = 0.98), LC (AUC = 0.88) or non-HCC (LC + CHB, AUC = 0.94) compared to the performance of double combinations or single biomarkers, respectively. Notably, among patients with AFP levels≤20 ng/μl, the double combination panel (TERT@miR-122) retains satisfactory diagnostic performance in discriminating HCC from the others (HCC vs. CHB, AUC = 0.96; HCC vs. LC, AUC = 0.88, HCC vs. non-HCC, AUC = 0.94). The triple combination panel AFP@TERT@miR-122 shows a better diagnostic performance for screening HCC in HBV patients, regardless of AFP levels. The newly established panels can be a potential application in clinical practice in Vietnamese setting.

Assessment of Knowledge and Practice on Hepatitis B Infection Prevention and Associated Factors among Health Science Students in Woldia University, Northeast Ethiopia.

Background Hepatitis B virus is a global problem, with 66% of all the world population living in areas where there are high levels of infection. HBV is the leading risk factor for HCC globally and accounts for at least 50% of cases of HCC. Medical and health science students, being part of the health-care system, are exposed to the infection as a risk as other health-care workers when they come in contact with patients and contaminated instruments. Objective The main aim of this study was to assess the knowledge and practice of hepatitis B virus infection prevention and its associated factors among health science students in Woldia University. Methods Institutional-based cross-sectional study was conducted from January 30 to May 30, 2019, among health science students of Woldia University who had previous clinical attachments. Two hundred students were selected by the systematic random sampling method. Association of dependent and independent variables was computed using a bivariable and multivariable logistic regression model. P<0.05 was considered as significantly associated. Result The study revealed that, out of 200 participants, 96 (48%) have poor knowledge, whereas 104 (52%) showed good knowledge about HBV. Regarding the practice of participants, 79 (39.5%) of the students have good practice to prevent HBV, whereas 121 (59.5%) had poor practice towards HBV infection prevention. Conclusion Based on the current study, greater than half of the students who participated in the study have good knowledge of hepatitis B infection prevention and most of the students have poor practice about infection prevention of hepatitis B virus.

ONCOLOGICAL CARE FOR THE PATIENTS WITH HEPATOCELLULAR CARCINOMA IN SVERDLOVSK REGION

HCC epidemiologic data in Sverdlovsk region are presented in current issue. 1293 of new cases of HCC were diagnosed since 2015 till 2019. The incidence rate of HCC in 2019 was 6,53 cases per 100000 people and standardized incidence ratio was 3,48 per 100000 people. The maximum of new cases was among the people older than 70 years. HCC developed in cirrhotic liver in 70,2% of cases. The main risk factors were virus hepatitis (49,6%), regular alcohol consumption (23%) and obesity (9,9%). The post-mortem diagnosis exceeds 40% of cases. The one-year mortality was 72-73%. The number of patients with HCC sent to the regional oncology dispensary increased in the last 5 years in 5 times. There were 124 of such patients in 2019. The majority has HCC at BCLC D stage (56,5%). Only 16,7% of patients received specialized treatment. The introduction of multidisciplinary team led to a doubling of annual number of treated patients with HCC.

The Recruitment of Innate Immune Cells in Liver Diseases: Uncovering the Role of NK Cells and pDC in HCC and NASH

Background/ ObjectiveHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, with over half a million new cases diagnosed annually worldwide. The fatality of HCC is high despite administration of traditional chemotherapies. In recent years, immunotherapy has become a promising strategy to treat cancer, such as PD‐1/PDL‐1 immune checkpoint blockade. However, the interactions between immune cells and HCC and how immunotherapies work, in vivo, in HCC are still unclear. Non‐alcoholic steatohepatitis (NASH) is an extremely severe form of fatty liver disease and often associated with heavy infiltration of immune cells. Natural Killer (NK) cells and plasmacytoid dendritic cells (pDC) are critical in the innate immune response, and are known for their cytotoxic and interferon producing abilities in response to cancer cells and viral pathogens, respectively. To learn more about the role of innate immunity in liver diseases, we evaluated and characterized pDC and NK cells in HCC and NASH compared to their background hepatic tissue.MethodsNK cells and pDC were isolated from HCC, NASH and hepatic tissue, stained with CD3, CD56, and CXCR6 or BDCA2 and CD123, respectively. The flow cytometry data were acquired and analyzed using FlowJo. E2‐2 immunostain for pDC was performed on FFPE tissue of HCC and NASH.ResultsThe presence of pDC was identified in the lymphoid aggregates of HCC and background cirrhotic areas (6/9 cases). In contrast, in 3 HCC cases, no pDCs were appreciated either in tumors or their backgrounds, including two patients who were smokers and with a history of coronary artery disease. In addition, using flow cytometry we demonstrated that there were more pDC in tumor infiltrating lymphocytes (TILs) of HCC compared to adjacent and distant hepatic tissues (Figure 1). We also found that NK cells isolated from NASH livers do not express CXCR6, a marker for liver‐resident NK cells, in contrast to NK cells obtained from HCC that express high levels of CXCR6 in both tumor and non‐tumor areas. The NK cells from NASH appear similar to those isolated and expanded from peripheral blood as both show low levels of CXCR6 (Figure 2). This suggests that NK cells in NASH originated from the blood and completely outnumber those in the liver, while the NK cells in HCC are residents of the liver.ConclusionsWe have shown that both pDC and NK cells are recruited to the liver in patients with NASH or HCC. More pDC were found in HCC tumors compared to surrounding hepatic tissue. NK cells isolated from NASH do not express CXCR6, a marker for liver‐resident NK cells. This study will further uncover the roles of innate immunity in liver disease and assist in the establishment of novel immunotherapies.A. pDC were present in the lymphoid aggregates of HCC and infiltrating tumor tissue.B. The numbers of pDC in TILs of HCC, adjacent and distant hepatic tissue.Figure 1Reduced expression of CXCR6 in NASH liverFigure 2