scholarly journals TGF-β1 polymorphism 509 C>T is associated with an increased risk for hepatocellular carcinoma in HCV-infected patients

2015 ◽  
Vol 14 (2) ◽  
pp. 4461-4468 ◽  
Author(s):  
J. Ma ◽  
Y.C. Liu ◽  
Y. Fang ◽  
Y. Cao ◽  
Z.L. Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Increased Risk ◽  
Tgf Β1

scholarly journals Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2499
Author(s):  
Lisanne Noordam ◽  
Zhouhong Ge ◽  
Hadiye Özturk ◽  
Michail Doukas ◽  
Shanta Mancham ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Occult Metastasis ◽  
Recurrence Rates ◽  
Curative Intent ◽  
Cancer Testis Antigens ◽  
Negative Prognostic Factor ◽  
Increased Risk ◽  
Hcc Recurrence ◽  
Cancer Testis

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.

scholarly journals Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nghiem Xuan Hoan ◽  
Pham Thi Minh Huyen ◽  
Mai Thanh Binh ◽  
Ngo Tat Trung ◽  
Dao Phuong Giang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Disease Progression ◽  
Infection Risk ◽  
Hbv Infection ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Programmed Cell Death 1

AbstractThe inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.

Attenuation of diethyl nitrosamine-induced hepatocellular carcinoma by taxifolin and/or alogliptin: The interplay between toll-like receptor 4, transforming growth factor beta-1, and apoptosis

2021 ◽  
pp. 096032712110084
Author(s):  
AM Kabel ◽  
HH Arab ◽  
MA Abd Elmaaboud
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transforming Growth Factor Beta ◽  
Caspase 3 ◽  
Transforming Growth Factor ◽  
Liver Function Tests ◽  
Toll Like Receptor ◽  
Caspase 9 ◽  
Toll Like Receptor 4 ◽  
Growth Factor Beta ◽  
Tgf Β1

Hepatocellular carcinoma (HCC) is the most common form of liver malignancies worldwide. Alogliptin is an anti-diabetic that may have effective anticancer properties against many types of malignancies. Taxifolin is a flavonoid that has potent antioxidant, and anti-inflammatory properties. The objective of this study was to explore the impact of alogliptin and/or taxifolin on diethyl nitrosamine-induced HCC in rats. One hundred male Wistar rats were divided into five equal groups as follows: Control; HCC; HCC + Alogliptin; HCC + Taxifolin; and HCC + Alogliptin + Taxifolin group. The survival rate, liver function tests, tissue antioxidant enzymes, malondialdehyde (MDA), nuclear factor (erythroid derived 2)-like 2 (Nrf2), transforming growth factor beta 1 (TGF-β1), interleukin 1 alpha (IL-1α), and toll-like receptor 4 (TLR4) were measured. Also, hepatic caspase 3, caspase 9, beclin-1, and c-Jun NH2-terminal kinase (JNK) in addition to serum alpha-fetoprotein (AFP) and α-L-Fucosidase (AFU) were assessed. Specimens of the liver were subjected to histopathological examination. Alogliptin and/or taxifolin induced significant improvement of liver function tests with significant increase in the survival rate, tissue antioxidant enzymes, Nrf2, caspase 3, caspase 9, Beclin-1 and JNK activities associated with significant decrease in serum AFP and AFU, tissue MDA, TGF-β1, IL-1α and TLR4 expression compared to HCC group. These results were significant with taxifolin/alogliptin combination when compared to the use of each of these agents alone. In conclusion, taxifolin/alogliptin combination might be used as adjuvant therapy for attenuation of HCC.

scholarly journals Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1023
Author(s):  
Eirini I. Rigopoulou ◽  
George N. Dalekos
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Diseases ◽  
Treatment Modalities ◽  
Primary Biliary Cholangitis ◽  
Autoimmune Liver Diseases ◽  
Increased Risk ◽  
Liver Cancers ◽  
Medium Risk ◽  
Causes Of Mortality

Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.

scholarly journals Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 210
Author(s):  
Martynas Ridziauskas ◽  
Birutė Zablockienė ◽  
Ligita Jančorienė ◽  
Artūras Samuilis ◽  
Rolandas Zablockis ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Liver Stiffness ◽  
Direct Acting Antiviral ◽  
End Of Treatment ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Direct Acting

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.

scholarly journals Combined Inhibition of TGF-β1-Induced EMT and PD-L1 Silencing Re-Sensitizes Hepatocellular Carcinoma to Sorafenib Treatment

2021 ◽  
Vol 10 (9) ◽  
pp. 1889
Author(s):  
Ritu Shrestha ◽  
Prashanth Prithviraj ◽  
Kim R. Bridle ◽  
Darrell H. G. Crawford ◽  
Aparna Jayachandran
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Treatment ◽  
Immune Checkpoint ◽  
Post Treatment ◽  
Immune Checkpoints ◽  
Sorafenib Treatment ◽  
Mesenchymal Transition ◽  
Immune Checkpoint Molecules ◽  
Tgf Β1 ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is the most common type of primary hepatic malignancy. HCC is one of the leading causes of cancer deaths worldwide. The oral multi-tyrosine kinase inhibitor Sorafenib is the standard first-line therapy in patients with advanced unresectable HCC. Despite the significant survival benefit in HCC patients post treatment with Sorafenib, many patients had progressive disease as a result of acquiring drug resistance. Circumventing resistance to Sorafenib by exploring and targeting possible molecular mechanisms and pathways is an area of active investigation worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process allowing epithelial cells to assume mesenchymal traits. HCC tumour cells undergo EMT to become immune evasive and develop resistance to Sorafenib treatment. Immune checkpoint molecules control immune escape in many tumours, including HCC. The aim of this study is to investigate whether combined inhibition of EMT and immune checkpoints can re-sensitise HCC to Sorafenib treatment. Post treatment with Sorafenib, HCC cells PLC/PRF/5 and Hep3B were monitored for induction of EMT and immune checkpoint molecules using quantitative reverse transcriptase (qRT)- PCR, western blot, immunofluorescence, and motility assays. The effect of combination treatment with SB431542, a specific inhibitor of the transforming growth factor (TGF)-β receptor kinase, and siRNA mediated knockdown of programmed cell death protein ligand-1 (PD-L1) on Sorafenib resistance was examined using a cell viability assay. We found that three days of Sorafenib treatment activated EMT with overexpression of TGF-β1 in both HCC cell lines. Following Sorafenib exposure, increase in the expression of PD-L1 and other immune checkpoints was observed. SB431542 blocked the TGF-β1-mediated EMT in HCC cells and also repressed PD-L1 expression. Likewise, knockdown of PD-L1 inhibited EMT. Moreover, the sensitivity of HCC cells to Sorafenib was enhanced by combining a blockade of EMT with SB431542 and knockdown of PD-L1 expression. Sorafenib-induced motility was attenuated with the combined treatment of SB431542 and PD-L1 knockdown. Our findings indicate that treatment with Sorafenib induces EMT and expression of immune checkpoint molecules, which contributes to Sorafenib resistance in HCC cells. Thus, the combination treatment strategy of inhibiting EMT and immune checkpoint molecules can re-sensitise HCC cells to Sorafenib.

Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation

1994 ◽  
Vol 20 (2) ◽  
pp. 218-222 ◽  
Author(s):  
Giorgio Ballardini ◽  
Paolo Groff ◽  
Marco Zoli ◽  
GianPaolo Bianchi ◽  
Fabrizio Giostra ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Increased Risk

scholarly journals Inpatient Outcomes and Rates of Venous Thromboembolism and Gastrointestinal Bleeding in Patients with Hepatocellular Carcinoma: Results from Nationwide Inpatient Sample Database 2007-2016

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2162-2162
Author(s):  
Kamelah Abushalha ◽  
Sawsan Abulaimoun ◽  
Ryan Walters ◽  
Sara Albagoush ◽  
Hussain I Rangoonwala ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Venous Thromboembolism ◽  
Gastrointestinal Bleeding ◽  
Hospital Mortality ◽  
Hospital Cost ◽  
Clinical Decision Making ◽  
Conflicts Of Interest ◽  
Increased Risk ◽  
Increasing Trend ◽  
Increasing Trends

Background: Patients with hepatocellular carcinoma (HCC) are at an increased risk for developing venous thromboembolism (VTE)- mainly portal venous thrombosis (PVT). Malignancy and liver cirrhosis ( 80%-90% of HCC cases are related to cirrhosis) are conditions that can perturb the hemostatic balance towards a prothrombotic state. Also, these patients with HCC are at high risk for gastrointestinal bleeding (GIB), making thromboprophylaxis and anticoagulation a treatment challenge. Additional information regarding the outcomes and severity of both VTE and GIB in patients with HCC would be useful to guide clinical decision-making Aim: To determine the rates, inpatient mortality, length of stay (LOS) and hospital cost of VTE and GIB-related admissions in patients with hepatocellular carcinoma. Method: We used ICD-9-CM and ICD-10-CM codes to identify hospitalizations from 2007 to 2016 that included HCC with primary discharge diagnoses of GIB or VTE. Linear trends in the rate of GIB and VTE, as well as in-hospital mortality, LOS, and inflation-adjusted hospital cost (in 2016 US dollars), were evaluated using Daniel's test; piecewise slopes were used as needed. All analyses accounted for the NIS sampling design with updated hospital trend weights used as appropriate. SAS v. 9.4 was used for all analyses. Results: Between 2007 and 2016, we identified 6,527,871 hospitalizations with HCC and a primary discharge diagnosis of GIB (3,517,059; 53.9%) or VTE (3,010,812; 46.1%). From 2007 to 2010, a decreasing trend was observed in the rate of GIB diagnoses (55.5% to 51.6%, ptrend < .001), whereas an increasing trend was observed for VTE diagnoses (44.5% to 48.4%, ptrend < .001). By contrast, from 2010 to 2016, an increasing trend was observed in GIB (51.6% to 55.2%, ptrend < .001), whereas a decreasing trend was observed in VTE (48.4% to 44.8%, ptrend < .001). For in-hospital mortality, a decreasing trend was observed for GIB (2.3% to 1.9%, ptrend < .001), whereas a decreasing trend was observed in VTE until 2012 (1.8% to 1.5%, ptrend < .001), after which no trend was indicated (1.5% to 1.6%, ptrend = .337). Although decreasing trends in LOS were observed for GIB (3.4 days to 3.2 days, ptrend < .001) and VTE (4.3 days to 3.3 days, ptrend < .001), increasing trends were observed for inflation-adjusted hospital cost for both GIB ($6,996 to $7,707, ptrend < .001) and VTE ($7,283 to $7,584, ptrend = .048). Conclusion: In this NIS cohort of hospitalized patients with HCC, GIB was more frequently observed than VTE. Trends observed in the rates of GIB and VTE went in opposite directions. In general decreasing trends were observed in in-hospital mortality and LOS for both VTE and GIB. By contrast, increasing trends were observed in the hospital cost for both diagnoses. Clinicians should balance benefits against risks when deciding VTE prophylaxis and treatment in patients with HCC. Future studies are needed to determine the ideal agent and specific dosages to treat HCC-associated VTE. Disclosures No relevant conflicts of interest to declare.

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