Dataset Information

Role of Lymphotoxin-α Gene Polymorphism in Hepatitis C Virus-Related Chronic Liver Disorders.

ABSTRACT:

Background

Tumor necrosis factor (TNF) family includes lymphotoxin-alpha (LTA) which is a pro-inflammatory cytokine which plays a role in hepatic fibrogenesis. LTA gene polymorphism plays a role in different inflammatory and immunomodulatory diseases. This polymorphism is also suggested to affect chronic hepatitis C (CHC) infection course.

Aim

To study the contribution of LTA gene polymorphism in different chronic hepatitis C stages and hepatocellular carcinoma risk.

Patients and methods

Our study included 108 chronic HCV patients grouped according to the disease stage. Group (A): CHC, group (B): liver cirrhosis (LC), group (C): LC with HCC, and group (D): healthy controls. Routine laboratory investigations, polymerase chain reaction (PCR) for quantification of HCV, abdominal ultrasonography, and Liver stiffness measurement (LSM) were done. Child-Turcotte-Pugh, Model for end-stage liver disease (MELD), and Fibrosis index based on 4 (FIB-4) scores were calculated. We used the PCR-restriction fragment length polymorphism technique for lymphotoxin-α genotyping.

Results

The A/G genotype was predominant in all groups. In HCC patients, G/G genotype was more frequent (31.8%) than in the LC group (19.4%), CHC group (17.8%), and controls (4.17%). A significant association was found between LTA genotypes and the child classes in HCC (P<0.01) but not in LC patients (P>0.05). HCC patients carrying A/G genotype had higher MELD scores than other genotypes. Multivariate binary logistic regression analysis confirmed that LTA G/G genotype and low platelet count were independent predictors for HCC development in patients with HCV-related LC.

Conclusion

Detection of LTA G/G genotype in chronic HCV patients could help to recognize high-risk patients for disease progression and HCC development.

SUBMITTER: Galal G

PROVIDER: S-EPMC8164674 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China. METHODS:We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated. RESULTS:A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P?<?0.01), septic shock (P?<?0.001), and ACLF-3 (P?<?0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P?<?0.01) and septic shock (P?<?0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P?<?0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection. CONCLUSIONS:Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.

Project description:BackgroundAcute-on-chronic liver failure (ACLF) is characterized by an excessive systemic inflammatory response and organ failure and has high mortality. Bacterial infections (BIs) worsen the clinical course of ACLF and carry a poor prognosis in ACLF patients. The efficacy of third-generation cephalosporins has been challenged in recent years. The aim of this study was to characterize the difference between ACLF patients with and without BIs and to provide a reference for medical intervention.MethodsA total of 140 patients with hepatitis B virus-related ACLF (HBV-ACLF) hospitalized at the Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai, China) between May 2013 and January 2020 were enrolled. Mann-Whitney U test was used to compare the baseline characteristics of HBV-ACLF patients with and without BIs. Univariate and multivariate analyses were performed to find predictors of BIs. The characteristics of BIs and the role of prophylactic antibiotics were profiled.ResultsA total of 97 episodes of BIs occurred in patients during the course of HBV-ACLF. Patients with and without BIs differed in clinical characteristics. The incidence of BIs showed a positive correlation with the ACLF grade (P = 0.003) and the clinical course (P = 0.003). The 90-day transplant-free survival of patients with BIs was lower than those without BIs (P < 0.0001). Patients administered prophylactic antibiotics showed a lower incidence of BIs and had a higher transplant-free survival probability than those who did not (P = 0.046). No statistical differences in antibiotic efficacy between third-generation and other antibiotics were observed (P = 0.108).ConclusionsBIs affected the clinical course and prognosis of patients with HBV-ACLF. Prophylactic antibiotics were of potential clinical importance in the prevention of BIs and improving the clinical course and prognosis in HBV-ACLF patients. Third-generation cephalosporins were qualified for use in antibiotic prophylaxis.