Programmed Death-Ligand 1 (PD-L1) Gene Polymorphisms as Predictive Markers for Development of Hepatocellular Carcinoma in Chronic Hepatitis C Virus Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Zainab Ahmed Ali- Eldin ◽  
Gamal El Attar ◽  
Hany Haroun Kaisar ◽  
Amira Isaac Samaan ◽  
Marwa Hassan ◽  
...  

Abstract Background Hepatocellular carcinoma is the sixth most common cause of cancer, and ranks fourth among the causes of cancer-related death. Major risk factors for HCC include chronic alcohol consumption, hepatitis B, hepatitis C and non-alcoholic fatty liver disease. Other, less common causes are Wilson’s disease, hereditary hemochromatosis, alpha1-antitrypsin deficiency, primary biliary cirrhosis and autoimmune hepatitis. Objective To investigate the associations of the genetic variants of PD-L1 (rs4143815 and rs2297136) with the risk of HCC in the Egyptian population. Patients and Methods This study was conducted in co-operation between Gastroenterology and Hepatology Department, Ain-Shams University and the Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute “between” March 2020 to July 2020. It included total participants of 138 Divided to Group (A): 35 normal people as control. Group (B): 51 patients with HCV infection and cirrhosis Group (c): 52 patients with HCV infection and cirrhosis with HCC. The patients were recruited from the outpatient clinic of Theodor Bilharz Research Institute Hospital (after consents were obtained). Results Also, the present study demonstrated that the functional polymorphisms (rs4143815) (CG) of the PD-L1 gene were associated with HCC risk as it is expressed in (53.3%) in HCC, (25.6%) in cirrhosis and (23.1%) in control group. And, rs4143815 (CG) show significant increase in Child C patients as (75%) Child C vs. (10%) Child A and (45%) was MELD/NA (20-29) vs. (10%) <9 with (61%) of patients were stage D in BCLC. There is significant increase in rs4143815 (CG) with age as 95% of gene positive patients more than 50years.With no significant in gender as 70% males and 30% females and there is no significant in smoking and DM. So, PDL-1 gene polymorphism rs4143815 (CG) could be used as a predictive marker for HCC after validation by larger studies or met analysis. Conclusion The present study demonstrated that the functional polymorphisms (rs4143815) (CG) of the PD-L1 gene were associated with HCC risk as it is expressed in (53.3%) of HCC, (25.6%) of cirrhosis and (23.1) % of control group. There is significant increase in rs4143815 (CG) with age as 95% of gene positive patients more than 50 years with no significance in gender smoking and DM. rs4143815 (CG) show significant increase in Child C patients as (75%) Child C vs. (10%) Child A and (45%) of patients was MELD/NA (20-29) vs. (10%) <9 and (70%) of patients were stage D in BCLC.

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S M Ghaly ◽  
I A Mohamed ◽  
N I Musa ◽  
O A Ahmed ◽  
A S Abuhalima ◽  
...  

Abstract Background hepatocellular carcinoma is the fifth most common tumor worldwide and the second most common cause of cancer-related death with a male-to-female predominance greater than 2:1. The presence of cirrhosis represents a key risk factor for the development of HCC. The prevalence of cirrhosis among patients with HCC has been estimated to be 85%-95% and the HCC incidence rate among patients with cirrhosis has been shown to be 2%-4% per year. HCV infection is a leading cause of liver cirrhosis and hence the development of HCC. Egypt has the highest HCV prevalence worldwide; with estimated rate of 10% of Egyptians between 15 – 59 years as reported by the Egyptian Health Issues Survey (EHIS) in 2015. Aim of the Work the aim of this study was to evaluate the impact of Direct Acting Antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection on recurrence of HCV related HCC after intervention. Patients and Methods this study was conducted on 50 patients with previously treated HCC who were treated for HCV infection using direct acting antiviral agents after confirming HCC regression and response to different treatment modalities and were followed for one year after antiviral treatment. A control group of another 50 patients with cured HCC who didn’t receive DAA therapy was included in the study to compare the recurrence rate in both groups and its relation to the antiviral therapy. Results the two groups didn’t differ as regards age, sex, biochemical profile, AFP, CBC and child score. The results of the study came to show an HCC recurrence rate of 38% in patients who received direct acting antiviral therapy after HCC intervention versus 62% in those who didn’t receive antiviral therapy. Conclusion direct acting antiviral drugs didn’t show to increase the risk of HCC recurrence in comparison to the control group. Yet it did not abolish it. So, close follow up of patients with HCC receiving antiviral therapy is highly recommended.


2014 ◽  
Vol 25 (6) ◽  
pp. 461-465
Author(s):  
João Paulo De Carli ◽  
Soluete Oliveira da Silva ◽  
Maria Salete Sandini Linden ◽  
Carmen Silvia Busin ◽  
Luiz Renato Paranhos ◽  
...  

The objective of this study was to evaluate the cellular proliferative potential of oral lichen planus (OLP) lesions from patients without hepatitis C virus (HCV) by means of AgNOR method, as well as the cellular proliferative potential of the normal oral mucosa from patients with HCV, treated or untreated by interferon and ribavirin. A cross-sectional study was developed to investigate four groups: 10 HCV+ patients without clinical signs of OLP who had never been treated for HCV infection - Group 1; 10 HCV+ patients that were under interferon and ribavirin treatment - Group 2; 15 patients with reticular OLP lesions histopathologically confirmed, without HCV - Group 3; and 15 blood donors without HCV infection and no clinical signs of OLP GROUP 4 Control Group. The cytological material of all groups was collected by the liquid-based cytology technique. Then, the sedimented material from each patient was filled with the Nucleolar Organizer Regions impregnation by silver method (AgNOR). The count of NORs was performed on 100 epithelial cell nuclei per patient using the Image Tool(tm) software. The Tukey HSD test was used to compare the median value of NORs among the groups and showed that the oral mucosa of HCV+ patients previously treated with anti-HCV drugs (GROUP 2), presented a higher average number of NORs in relation to others (p<0.05). The anti-HCV treatment may be related to increased cell proliferation of oral mucosa, indicating a possible relationship between OLP and HCV+ patients treated with interferon and ribavirin.


2006 ◽  
Vol 290 (5) ◽  
pp. G847-G851 ◽  
Author(s):  
Jinah Choi ◽  
J.-H. James Ou

Hepatitis C virus (HCV) is a major cause of viral hepatitis that can progress to hepatic fibrosis, steatosis, hepatocellular carcinoma, and liver failure. HCV infection is characterized by a systemic oxidative stress that is most likely caused by a combination of chronic inflammation, iron overload, liver damage, and proteins encoded by HCV. The increased generation of reactive oxygen and nitrogen species, together with the decreased antioxidant defense, promotes the development and progression of hepatic and extrahepatic complications of HCV infection. This review discusses the possible mechanisms of HCV-induced oxidative stress and its role in HCV pathogenesis.


2011 ◽  
Vol 140 (5) ◽  
pp. S-924-S-925 ◽  
Author(s):  
Hillary Lin ◽  
Nghiem B. Ha ◽  
Deawodi Ladzekpo ◽  
Aijaz Ahmed ◽  
Walid Ayoub ◽  
...  

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S329-S329 ◽  
Author(s):  
Leila Hojat ◽  
David Kaelber ◽  
Ann Avery

Abstract Background Hepatitis C virus (HCV) infection is a major public health burden. The USPSTF and CDC have both released guidelines which recommend screening the baby boomer population (individuals born between 1945 and 1965) given the overrepresentation of HCV infection in this cohort. However, screening rates remain low despite prior attempts at improvement. Objective To improve HCV testing rate in the birth cohort in compliance with national guidelines without increasing primary care provider workload or alert fatigue. Methods We developed a population health initiative that employed EHR-based tools involving direct patient messaging and bulk lab test ordering via a personal electronic health portal system. This was completed independent of a face-to-face interaction between the patient and provider. Results We collected data on 1,024 patients total (514 in the intervention group and 510 in the control group) over a 12-week period. We found a statistically significant higher test completion rate within the intervention group vs. the control group after this initiative was launched: 33.7% in the intervention group (173/514) vs. 19.0% in the control group (97/510) (p-value &lt;0.0002, OR 2.16, 95% CI 1.62–2.88). Bulk lab ordering appeared to have a large impact while bulk messaging appeared to have a less significant role. Conclusion To our knowledge, this is the first EHR-based population health initiative to involve obtaining blood work without a direct face-to-face encounter between the provider and patient. This methodology has a broad range of applications including any recommended screening or disease-specific testing, and it will be essential for health systems to adopt similar protocols as we progress toward a pay-for-performance reimbursement model. Disclosures All authors: No reported disclosures.


2018 ◽  
Vol 17 (5) ◽  
pp. 0-10
Author(s):  
Mahmoud El-Bendary ◽  
Mustafa Neamatallah ◽  
Hatem Elalfy ◽  
Tarek Besheer ◽  
Emily Kamel ◽  
...  

Introduction and aim. Hepatitis C virus (HCV) infection is a global medical problem. HLA –DRB1 alleles have an important role in immune response against HCV. The aim of this study is to clarify the contribution of HLA –DRB1 alleles in HCV susceptibility in a multicentre family-based study. Material and methods. A total of 162 Egyptian families were recruited in this study with a total of 951 individuals (255 with chronic hepatitis C (CHC), 588 persons in the control group(-ve household contact to HCV) and 108 persons who spontaneously cleared the virus (SVC). All subjects were genotyped for HLA -DRB1 alleles by SSP-PCR and sequence based typing (SBT) methods. Results. The carriage of alleles 3:01:01 and 13:01:01 were highly significant in CHC when compared to that of control and SVC groups [OR of 3 family = 5.1289, PC (Bonferroni correction ) = 0.0002 and 5.9847, PC = 0.0001 and OR of 13 family = 4.6860, PC = 0.0002 and OR = 6.5987, PC = 0.0001 respectively]. While DRB1*040501, DRB1*040101, DRB1*7:01:01 and DRB1*110101 alleles were more frequent in SVC group than CHC patients (OR = 0.4052, PC = 0.03, OR: OR = 0.0916, PC = 0.0006, OR = 0.1833, PC = 0.0006 and OR = 0.4061, PC = 0.0001 respectively). Conclusions. It was concluded that among the Egyptian families, HLA- DRB1*030101, and DRB1*130101 alleles associated with the risk of progression to CHC infection, while DRB1*040101, DRB1*040501, DRB1*7:01:01and DRB1*110101 act as protective alleles against HCV infection.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4668-4668
Author(s):  
Janet G. Grudeva

Backgroud: An increasing number of bacterial and viral infections have been linked with specific subtypes of lymphoma. Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as a subset of B-cell non-Hodgkin, s lymphomas (B-NHL), often with extranodal localization. Design and methods: The study was conducted in the Department of Hematology and consisted 149 (86 male, 63 female) untreated patients with a new diagnosis of B-NHL for 5-years period (2000–2004). HCV infection was investigated by testing for HCV antibodies in serum samples. The controls were 587 patients (without intravenous drug users) in other departments of the same hospital. Results: HCV infection was documented in 13 cases (8,4%) with NHL. The infected patients were not clinically relevant cryoglobulinemic activity, increased rate of autoimmune disorders and extranodal localizations prevalence. There was statistically significant difference between the NHL and control group (p<0,01) and no statistically significant difference between man/women carriers (p>0,05) into the NHL group. Overall, the clinical outcome of HCV-positive NHL does not seem to be different from that of NHL patients without HCV infection. However, the evidence of a significant liver injury may predict a worse prognosis in these cases. Conclusions: Our date suggest that HCV infection may be associated with B-NHL. With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most date support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus.


2016 ◽  
Vol 34 (6) ◽  
pp. 650-653 ◽  
Author(s):  
Norihisa Yada ◽  
Toshiharu Sakurai ◽  
Tomohiro Minami ◽  
Tadaaki Arizumi ◽  
Masahiro Takita ◽  
...  

Objective: We have reported about real-time tissue elastography (RTE), which displays relative strain by measuring the relative distortion of the tissue, and found this information to be useful for diagnosing liver fibrosis. However, its use in predicting hepatocellular carcinoma has not been reported as yet. Here, we investigated RTE to predict liver carcinogenesis in patients with chronic hepatitis C virus (HCV) infection. Methods: We enrolled 160 patients with chronic HCV, who were followed up for 39.9 ± 22.9 weeks (median). They underwent RTE and then ultrasounds every 3-6 months. Results: Respective cumulative liver cancer incidences for years 1, 2, 3, 4, and 5 were, for the entire cohort: 2.0, 5.6, 8.8, 13.1, and 23.9%; for those whose liver fibrosis index (LFI) was ≤2.0: 0.0, 0.0, 0.0, 0.0, and 0.0%; for those whose LFI was 2-2.8: 0.0, 7.4, 7.4, 13.2 and 19.9%; and for those whose LFI was >2.8: 12.9, 12.9, 21.7, 31.4, and 31.4% (p = 0.011; log-rank test). Conclusions: Measurements of LFI by strain imaging can effectively predict liver cancer risk in patients with chronic HCV infection.


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