Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs.

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023-0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.

Efficacy of Antiseptic Solutions in Treatment of Staphylococcus Aureus Infected Surgical Wounds with Patches of Vascular Graft: An Experimental Study in Rats.

Background and objectives: Treatment of a prosthetic vascular graft infection (PVGI) remains a challenging problem in vascular surgery. The aim of this study was to design a novel rat model for treatment of peripheral vascular prosthesis infection caused by Staphylococcus aureus (S. aureus) and to determine the efficacy of different antiseptic solutions in suppressing or eradicating infection from the wound and the graft material itself. Materials and methods: A piece of Dacron vascular prosthesis was surgically implanted at the dorsum of 48 Wistar rats and the wounds were infected with 5 McFarland standard inoculum of S. aureus. Suppurating wounds were daily irrigated with different antiseptic solutions: octenidine dihydrochloride, povidone-iodine, chlorhexidine digluconate, and sterile saline. The antimicrobial action of antiseptics was defined according to their capability to eradicate bacteria from the graft surroundings and bacteriological examination of the graft itself. Extended studies on wound microbiology, cytology, and histopathology were performed with an additional group of 10 rats, treated with the most effective antiseptic-octenidine dihydrochloride. Results: Four-day treatment course with octenidine, povidone-iodine, and chlorhexidine resulted in 99.98% (p = 0.0005), 90.73% (p = 0.002), and 65.97% (p = 0.004) decrease in S. aureus colonies in wound washouts, respectively. The number of S. aureus colonies increased insignificantly by 19.72% (p = 0.765) in control group. Seven-day treatment course with octenidine eradicated viable bacteria from nine out of 10 wound washouts and sterilized one vascular graft. Conclusions: A reproducible rat model of PVGI with a thriving S. aureus infection was designed. It is a first PVGI animal model where different antiseptic solutions were applied as daily irrigations to treat peripheral PVGI. Seven-day treatment with octenidine eradicated bacteria from the wound washouts for 90% of rats and one vascular graft. Further studies are needed to investigate if irrigations with octenidine could properly cure vascular bed from infection to assure a successful implantation of a new synthetic vascular substitute.

New in vitro model evaluating antiseptics' efficacy in biofilm-associated Staphylococcus aureus prosthetic vascular graft infection.

PURPOSE: To develop a new in vitro model of prosthetic vascular graft infection (PVGI) and evaluate antimicrobial and biofilm-disrupting efficacy of 0.1% octenidine dihydrochloride, 10% povidone-iodine and 0.02% chlorhexidine digluconate against biofilm-producing Staphylococcus aureus (S. aureus). METHODOLOGY: The effect of antiseptics on the microscopic integrity and antimicrobial effect on S. aureus biofilms was tested by growing biofilms on glass coverslips, in the modified Lubbock chronic wound pathogenic biofilm (LCWPB) model and on the surface of vascular grafts using qualitive and quantitative methods as well as by scanning electron microscopy (SEM). RESULTS: Chlorhexidine worked best on destroying the integrity of S. aureus biofilms (P=0.002). In the LCWPB model, octenidine and povidone-iodine eradicated all S. aureus colonies (from 1.79 × 109 c.f.u. ml-1 to 0). In the newly developed PVGI model, the grafts were successfully colonized with biofilms as seen in SEM images. All antiseptics demonstrated significant antimicrobial efficacy, decreasing colony counts by seven orders of magnitude (P=0.002). Octenidine was superior to povidone-iodine (P=0.009) and chlorhexidine (P=0.041). CONCLUSION: We implemented an innovative in vitro model on S. aureus biofilms grown in different settings, including a clinically challenging situation of PVGI. The strongest antimicrobial activity against S. aureus biofilms, grown on prosthetic vascular grafts, was showed by 0.1% octenidine dihydrochloride. We suggest that combinational therapy of antiseptics between chlorhexidine with either povidone-iodine or octenidine dihydrochloride should be tested in further experiments. Despite the need of further studies, our findings of these in vitro experiments will assist the management of vascular graft infection in clinical cases.