Hepatitis C virus (HCV) is one of major etiologies of hepatocellular carcinoma (HCC) worldwide. HCC is a highly prevalent and deadly cancer because of high risks of recurrence and/or metastasis. ...Identification of potential prognostic markers and/or target molecules could help in the preventing and managing HCV‐related HCC after the success of DAA treatment. Extracellular exosomes contain numerous signaling molecules including lncRNAs and play an important role in intercellular communication. To develop of liquid biopsy for prognostic markers of Hepatitis C Virus‐related hepatocellular carcinoma after surgical resection, we determined DANCR expression level in circulating exosomes. Total exosomes were extracted from 200 μL of serum by exosome precipitation solution and quantification DANCR by qPCR analysis. Results indicates exosomes DANCR levels was significantly higher among HCV‐related HCC patients with post‐resection recurrence than those without. Higher versus low exosomes DANCR with cut‐off at −7.5dCt lncDANCR‐U6) could predict HCV‐HCC recurrence (area under curve: 0.83). The 5‐y cumulative incidence of recurrence and mortality was 90.0% and 37.7%, respectively, among patients with higher exosomes DANCR, compared to 39.5% and 20.6%, respectively, among those with lower exosomes DANCR with harzard ratio (CI) of 3.8 (2.52–5.84) and 2.2 (1.29–3.89), respectively, by Cox regression model. The diagnostic power for HCC recurrence among HCV‐HCC patients was better with exosomes DANCR than with hepatic tumor DANCR or Tumor/Non‐tumor DANCR ratio. By knockdown or overexpression of DANCR in JFHlo (long‐term HCV‐infectious) cell models, we observed that increased DANCR enhanced cell migration and invasion ability by regulating mesenchymal‐associated β‐catenin expression. In this study, we demonstrated that circulating exosomes lnc‐DANCR could serve as a liquid biopsy for prognostic biomarker of HCC recurrence after surgical resection for HCV‐HCC.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Background/Aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the ...complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.
Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.
Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).
Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs. (Clin Mol Hepatol 2021;27:186-196)
The clinical significance of coinfection of SENV-H among patients with chronic hepatitis C (CHC) and the response to combination therapy with high-dose interferon-alpha (IFN) plus ribavirin in Taiwan ...are uncertain. A total of 151 (120 histologically proved) naı̈ve CHC patients who received 6 MU IFN thrice a week plus ribavirin for 24 weeks therapy were enrolled in this study. SENV-H DNA was tested by PCR method. Of 151 patients, 29 (19.2%) were positive for SENV-H DNA. The positive SENV-H DNA was significantly associated with HCV genotype 1b than non-1b infection (69.0% versus 43.4%;
P = 0.011). No other clinical, histopathological and virological factor was related to positive SENV-H DNA. After combination therapy, the rate of sustained viral response (SVR) of HCV and SENV-H were 66.9 and 78.3%, respectively. By multivariate analyses, the significant factors associated with HCV SVR after combination therapy were HCV genotype non-1b, pretreatment HCV RNA levels less than 200,000
IU/mL, and younger age. We conclude that coexistent SENV-H infection, apparently associated with HCV genotype 1b, is found among 19.2% of Taiwanese CHC patients. Both HCV and SENV-H are highly susceptible to combination therapy with high dose IFN and ribavirin and SENV-H coinfection does not affect the HCV response.
The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed ...by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1‐year‐olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year‐to‐year decrease in new HCV‐ and HBV‐related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.
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