Purpose It is unclear whether and how the long-term risk of hepatocellular carcinoma (HCC) will change in hepatitis C virus (HCV) infected patients who have reached sustained virologic response (SVR) with direct-acting antivirals (DAA). In this study, we assessed the long-term risk of HCC up to 10 years after SVR using fibrosis 4 score (FIB-4) and its dynamic changes. Patients and Methods A total of 701 DAA-treated patients who achieved SVR between January 2012 to October 2020 were enrolled in the study. The FIB-4 score of each patient was measured at the date of SVR and each follow-up visit annually. Patients were followed until December 31, 2021, with the longest follow-up time being 9.82 years. Results Following SVR, 27 cases of HCC were observed. The annual incidence rate of HCC remained stable with no obvious downward trend. Patients with a FIB-4 >3.25 at baseline or anytime during follow-up were at a higher risk of developing HCC than those whose FIB-4 remained below 3.25. Patients with cirrhosis and patients with no cirrhosis but a FIB-4 >3.25 were at higher risk of developing HCC than patients with no cirrhosis and a FIB-4 ≦3.25. Conclusion FIB-4 >3.25 measured at SVR or any time post-SVR was associated with HCC risks. The repeated measurement of FIB-4 revealed a better predictive ability of HCC risks than the simple measurement of FIB-4 at baseline. The additional stratification of patients by combining FIB-4 and cirrhosis leads to more accurately identifying high-risk patients. Surveillance of HCC is recommended for virologically cured patients with a FIB-4 >3.25 at SVR or anytime afterward and patients diagnosed with cirrhosis.
Objective: We explore the candidate susceptibility genes for influenza A virus (IAV), measles, rubella, and mumps and their underlying biological mechanisms.Methods: We downloaded the genome-wide association study summary data of four virus-specific immunoglobulin G (IgG) level data sets (anti-IAV IgG, anti-measles IgG, anti-rubella IgG, and anti-mumps virus IgG levels) and integrated them with reference models of three potential tissues from the Genotype-Tissue Expression (GTEx) project, namely, whole blood, lung, and transformed fibroblast cells, to identify genes whose expression is predicted to be associated with IAV, measles, mumps, and rubella.Results: We identified 19 significant genes (ULK4, AC010132.11, SURF1, NIPAL2, TRAP1, TAF1C, AC000078.5, RP4-639F20.1, RMDN2, ATP1B3, SRSF12, RP11-477D19.2, TFB1M, XXyac-YX65C7_A.2, TAF1C, PCGF2, and BNIP1) associated with IAV at a Bonferroni-corrected threshold of p < 0.05; 14 significant genes (SOAT1, COLGALT2, AC021860.1, HCG11, METTL21B, MRPL10, GSTM4, PAQR6, RP11-617D20.1, SNX8, METTL21B, ANKRD27, CBWD2, and TSFM) associated with measles at a Bonferroni-corrected threshold of p < 0.05; 15 significant genes (MTOR, LAMC1, TRIM38, U91328.21, POLR2J, SCRN2, Smpd4, UBN1, CNTROB, SCRN2, HOXB-AS1, SLC14A1, AC007566.10, AC093668.2, and CPD) associated with mumps at a Bonferroni-corrected threshold of p < 0.05; and 13 significant genes (JAGN1, RRP12, RP11-452K12.7, CASP7, AP3S2, IL17RC, FAM86HP, AMACR, RRP12, PPP2R1B, C11orf1, DLAT, and TMEM117) associated with rubella at a Bonferroni-corrected threshold of p < 0.05.Conclusions: We have identified several candidate genes for IAV, measles, mumps, and rubella in multiple tissues. Our research may further our understanding of the pathogenesis of infectious respiratory diseases.
The De Ritis ratio has good diagnostic accuracy in patients with chronic viral liver disease. However, its prognostic utility has remained controversial. This study was to identify different trajectories of De Ritis ratio in those hepatitis C patients cured and analyze relationship between trajectory groups and risk of hepatocellular carcinoma (HCC) with liver-related mortality by the retrospective cohort study. This retrospective longitudinal cohort included 1241 patients with hepatitis C underwent antiviral therapy since follow-up in 2012. De Ritis ratio trajectories were identified by the latent class growth mixed model. Patients were grouped into subgroups by De Ritis ratio according to longitudinal trajectories. The end points were HCC and liver-related mortality. Three distinct trajectory groups were characterized for serum De Ritis ratio: low-stable, middle-stable, and high-rising. 51 HCC and 11 liver-related mortality were recorded and tracked. Comparing to the low-stable group, the adjusted hazard ratios (HRs) and 95% confidence interval (CI) associated with HCC and liver-related mortality were 2.02 (1.12-3.63), 9.36 (3.61-24.29), for the middle-stable, and high-rising group, respectively. Notably, the high-rising trajectory group still had prognostic significance after adjusting for preoperative levels. Likewise, for the high-rising trajectory group of SVR, the HRs (95% CI) were 2.85 (1.03-10.75) for HCC and liver-related mortality, and in patients with cirrhosis, the HRs (95% CI) were 3.44 (1.64-7.19) and 4.35 (1.27- 14.84) in the middle-stable trajectory group and the high-rising trajectory group, respectively. The dynamic measurements of De Ritis ratio are recommended to monitor the prognosis of Hepatitis C patients.
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