MATERIALS AND METHODS: This is a retrospective study on patients with newly diagnosed hepatocellular carcinoma (HCC) at the University Malaya Medical Centre between 2011 and 2014. Survival times were analysed using the Kaplan- Meier procedure and comparison between groups was done using the log rank test.
RESULTS: The data of 190 patients was analysed. Chronic hepatitis B was the most common aetiology for HCC (43.7%), but a large proportion was cryptogenic or non-alcoholic steatohepatitis-related (41.6%). Only 11.1% were diagnosed early (BCLC Stage 0-A) while majority were diagnosed at an intermediate stage (BCLC Stage B, 53.7%). The median survival rate was significantly different between the different groups when either of the staging systems was used (p<0.05 for all comparisons). However, the two staging systems lacked agreement (weighted kappa 0.519, 95%CI: 0.449, 0.589) with significant difference in median survival rates between BCLC Stage A and HKLC Stage 2, and between BCLC Stage C and HKLC Stage 4.
CONCLUSION: Both staging systems were able to stratify patients according to survival, but they only had moderate agreement with significant differences observed in two groups of the staging systems.
METHODOLOGY: This is a prospective study where patients (n=119) blood was tested for anti-HAVIgG and CYP3A4*18 polymorphism.
RESULTS: The overall anti-HAV seroprevalence was 88.2%. The etiology of CLD was hepatitis B in 96 patients (80.7%) and hepatitis C in 23 patients (19.3%). There was a significant increase in the age of the prevalence of this disease after 30 years of age (p=0.008). CYP3A4*18 polymorphism was detected in 3 (2.5%) of the patients with chronic liver disease. However, there was no significant association between CP3A4*18 mutation and anti-HAV serology.
CONCLUSIONS: Age was the most important factor in determining anti-HAV positivity. It is concluded that CYP3A4*18 genetic polymorphism does not play a main role in influencing the seroprevalence of anti-hepatitis A among chronic viral hepatitis B and C liver disease patients.
METHODS: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression.
RESULTS: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL.
CONCLUSION: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.
OBJECTIVE: To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the infection.
METHODS: We recruited a total of 120 patients, 40 of whom from cirrhotic, 40 non-cirrhotic, and 40 acute flare chronic hepatitis B and 40 healthy controls. For all groups total cellular RNA was extracted from whole blood samples, genomic DNA was eliminated, and cDNA was synthesized using the RT2 first strand kit, as instructed by the manufacturer. The real-time profiler PCR array was performed on a master cycler ep realplex and the data were analyzed using an online data analysis software.
RESULTS: Non-cirrhotic chronic hepatitis B patients were found to significantly upregulate interleukin 10 receptors that regulate the balance between T helpers 1 and 2. On the other hand, patients with cirrhosis were found to have significant upregulated interleukin 3 gene expression.
CONCLUSION: Our finding suggests that upregulation of anti-inflammatory and downregulation of pro-inflammatory cytokines may play a role in the progression of non-cirrhotic chronic hepatitis B patients to cirrhotic and acute flare. However, a multi-center study with a larger sample size is needed to confirm our findings.
Objectives: This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection.
Methods: Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test.
Results: Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).
Conclusion: This study revealed that genetic diversity was found to have a significant impact on the severity of infection.