Polymorphisms of UGT1A7 and XRCC1 are associated with an increased risk of hepatocellular carcinoma in Northeast China

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.

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

Scientific Reports ◽

10.1038/s41598-021-87537-9 ◽

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.

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

Cancers ◽

10.3390/cancers13051023 ◽

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.

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

Medicina ◽

10.3390/medicina57030210 ◽

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.

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

Genetics and Molecular Research ◽

10.4238/2015.may.4.3 ◽

2015 ◽

Vol 14 (2) ◽

pp. 4461-4468 ◽

Cited By ~ 14

Author(s):

J. Ma ◽

Y.C. Liu ◽

Y. Fang ◽

Y. Cao ◽

Z.L. Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Increased Risk ◽

Tgf Β1

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

Journal of Hepatology ◽

10.1016/s0168-8278(05)80061-3 ◽

1994 ◽

Vol 20 (2) ◽

pp. 218-222 ◽

Cited By ~ 49

Author(s):

Giorgio Ballardini ◽

Paolo Groff ◽

Marco Zoli ◽

GianPaolo Bianchi ◽

Fabrizio Giostra ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Increased Risk

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

Blood ◽

10.1182/blood-2019-132018 ◽

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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Genetic Polymorphism of Glutathione S Transferases M1 and T1 in Indian Patients with Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2010/328408 ◽

2010 ◽

Vol 28 (6) ◽

pp. 369-376 ◽

Cited By ~ 15

Author(s):

Mohammad Asim ◽

Luqman A. Khan ◽

S. A. Husain ◽

Sajid Husain ◽

Manash P. Sarma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Alcohol Consumption ◽

Liver Cancer ◽

Cigarette Smoking ◽

Case Control Study ◽

Smoking Habit ◽

Case Control ◽

Gstt1 Null Genotype ◽

Increased Risk ◽

Control Study

Objective:Our aim was to evaluate whether the association of GSTM1/T1 gene polymorphisms modifies the risk of Hepatocellular carcinoma (HCC) and what is its correlation with other predisposing risk factors like alcohol intake, cigarette smoking and hepatitis B and C infections.Study design/setting:It was a case-control study, included 254 HCC cases compared with 525 hospital-based age and sex matched cases of chronic liver disease without HCC as controls from Indian population. The GSTM1 and GSTT1 genotypes were detected using conventional multiplex PCR method.Results:In this case-control study, we observed a positive correlation between age, HBV and HCV infection, smoking habit of > 20 packs/year, alcohol consumption of > 100 g/day and risk of liver cancer. We found significantly increased risk associated with GSTM1 null genotype (OR = 3.49; 95% CI = 2.52–4.84) as well as GSTT1 null genotype (OR = 3.12; 95% CI = 2.19–4.45), respectively. However, an increased risk of HCC was observed among heavy drinkers with GSTM1 (OR = 2.01; 95% CI = 1.11–3.66). Further, cigarette smoking showed a non-significant association with GSTT1 (OR = 1.49; CI = 0.69–3.25).Conclusion:Our results suggest that the variants in low penetrance gene such as GSTM1 and GSTT1 are associated with an increased liver cancer risk. Further, an influence of GSTM1/T1 null genotypes may contribute in the etiology of HCC in patients with higher cigarette and alcohol consumption.

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