A Case Report of Direct‐Acting Antiviral Therapy for Chronic Hepatitis C in a Patient With Dementia Treated in Collaboration With Multiple Specialists

Ribonucleic acid (RNA) viruses form populations with a high degree of genetic diversity, which facilitates adaptation to most changes in the environmental conditions. Therapeutic treatments are a type of change in the selective pressures to which RNA viruses also try to adapt. The selection of drug‐resistant mutants and escape mutants able to evade the immune response of the host are clear examples of the capacity of RNA viruses to maintain their infectivity in the presence of inhibitors. Therefore, it is increasingly evident that to find successful control measures for RNA viruses it is necessary to take into account the adaptive potential of these pathogens. Combination therapies and multiepitopic vaccines are antiviral strategies that have demonstrated their effectiveness. Another promising approach, referred to as lethal mutagenesis, exploits the high error rates of RNA viruses to push them above an error threshold incompatible with viability. Key Concepts: RNA viruses cause diseases that can be very difficult to treat. RNA viruses replicate their genomes with a very high error rate, giving rise to populations that contain a large genetic diversity. RNA viruses possess a great adaptive capacity that permits them to rapidly generate drug‐resistant mutants, as well as antibody or cytotoxic T lymphocyte escape mutants. The development of strategies for the control of RNA viruses must take into account their adaptive potential. One of the most successful strategies to control RNA viruses is the use of combination therapies. Lethal mutagenesis is a new antiviral therapy, which consists in the artificial increase of the virus error rate above a limit that is incompatible with viability.

Aim. The purpose of the article is to devise the method for predicting the development of lipid distress syndrome in patients with a sustained response to antiviral therapy of chronic viral hepatitis C on the basis of clinical and laboratory data.
 Materials and methods. The outcomes of lipid distress syndrome were studied in 235 patients with a sustained virological response to antiviral therapy of chronic hepatitis C during the follow-up period lasting from 1 to 10 years.
 Results. From the perspective of the discriminative analysis of the data of the complex examination of 135 patients, we developed a discriminative model of predicting the development of lipid distress syndrome in patients with a sustained response to antiviral therapy of chronic hepatitis C. The cross-checking of the accuracy of prediction was carried out by the examination of other 100 patients.
 Conclusion. Sensitivity, specificity, prognostic value of positive and negative prognostic results and the accuracy index of the developed discriminative model for predicting the development of lipid distress syndrome are equal to 100%.

The aim. is to develop a method, for predicting the development of lipid, distress syndrome in patients with a sustained, response to antiviral therapy of chronic viral hepatitis C on the basis of clinical and laboratory data. Materials and. methods . The outcomes of lipid, distress syndrome were studied in 235 patients with a sustained vi-rological response to antiviral therapy of chronic hepatitis C during the follow-up period, from 1 to 10 years. Results. On the basis of discriminant analysis of the data of complex examination of 135 patients, a discriminant model of predicting the development of lipid distress syndrome in patients with a sustained response to antiviral therapy of chronic hepatitis C. On the basis of the data of the survey of other 100 patients, cross-checking the accuracy of the prediction. was carried out. Conclusion. Developed, diskriminantnaja model allows by identifying 5 of biochemical and. immunological parameters of blood (low-density lipoproteins cholesterol, homocysteine, interleukin. 4 and. 10, TNF) to predict the development of lipid distress syndrome in patients with sustained response to antiviral therapy for chronic hepatitis С . The sensitivity, specificity, predictive value of positive and. negative results of forecasting and precision index developed forecasting model of Fisher discriminant lipid, distress syndrome equal 100%. The proposed, method, should, be used, in clinical practice to predict development of lipid, distress syndrome in patients with sustained, response to antiviral therapy for chronic hepatitis C.

Patient-reported symptoms during and after direct-acting antiviral therapies for chronic hepatitis C: The PROP UP study

The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.

There is limited data on the efficacy and safety of directly acting antiviral therapy (DAA) for chronic hepatitis C in pediatric population. The aim was to assess the efficacy and safety of DAA in chronic hepatitis C β-thalassemic major pediatric patients. Prospective study was conducted from September 2015 to January 2017. All β-thalassemic major chronic hepatitis C pediatric patients with age between 5 and 14 years were included in this study. Data related to demography, laboratory parameters, hepatitis C viral load, genotype and outcome of antiviral therapy was analyzed. DAA was planned according to EASL guidelines 2015 for chronic hepatitis C therapy in adults. Fourteen β-thalassemic major patients (median age was 9.5 y, 12 male) were studied. All patients were of genotype 3, received DAA (sofosbuvir 400 mg+daclatasvir 80 mg) for 12 weeks. The median viral load was 2.5×10 IU/mL. End of treatment response and sustained virological response at 12 weeks was achieved in all the patients. Serum alanine aminotransferase, aspartate aminotransferase, ferritin, and albumin significantly reduced after DAA. DAA in adult dosage are safe and effective for treatment of chronic hepatitis C (genotype 3) in pediatric β-thalassemic major population.

Is there sufficient evidence to recommend antiviral therapy in hepatitis C?

Intrahepatic Hepatitis B Virus Covalently Closed Circular DNA Can Be a Predictor of Sustained Response to Therapy

Economic and clinical effects of evaluating rapid viral response to peginterferon alfa-2b plus ribavirin for the initial treatment of chronic hepatitis C

Evaluation of 12-wk viral response to initial antiviral therapy for chronic hepatitis C has been recommended to minimize antiviral-associated morbidity and costs. The aim of this study was to examine the economic and clinical effects of evaluating rapid viral response during antiviral therapy for treatment naive chronic hepatitis C patients. We applied viral response and drug dosage from an international randomized clinical trial of ribavirin plus peginterferon alfa-2b or ribavirin plus interferon alfa-2b to a previously published computer cohort simulation to project lifelong clinical and economic outcomes. Natural history and economic estimates were based on published literature, expert panel estimates, and actual variable and reimbursement cost data. The assessment of 12-wk rapid viral response reduced antiviral treatment duration by 40-44% and antiviral costs by 44-45% (savings of $15,116-16,268 for peginterferon plus ribavirin and $8300 for interferon plus ribavirin) compared to full 48-wk dosing. With the 12-wk evaluation, the marginal cost-effectiveness of peginterferon plus ribavirin versus interferon plus ribavirin was $13,600-22,800 compared with $14,600-25,000 per discounted quality adjusted life-year gained with the 24-wk evaluation. For genotype 1, hepatitis C infected patients, 12-wk testing for peginterferon plus ribavirin remaining preferred and cost-effective compared with interferon plus ribavirin. For genotype 2 or 3, hepatitis C infected patients, 12-wk testing yielded similar results to those of 24-wk treatment. Assessment of 12-wk viral response in genotype 1, hepatitis C infected patients should reduce peginterferon plus ribavirin morbidity and costs and improve its cost-effectiveness; however, for genotype 2 and 3, hepatitis C infected patients, 12-wk testing and 24-wk treatment have similar outcomes. Decisions regarding continuation of antiviral treatment should also consider the variability in the accuracy of quantitative viral assays as well as patient preferences and other potential benefits of the same treatments.

Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p < 0.001), and the prevalence of early-stage HCC, including stage 0 and stage A Barcelona Clinic Liver Cancer, was significantly higher (52.9% versus 33.6%, p < 0.001). In nonviral HCC group, alcohol use was more common (39.9% versus 30.1%, p < 0.001), the prevalence of type 2 diabetes mellitus (T2DM) was higher (54.5% versus 35.1%, p < 0.001), and obesity was common (25.0% versus 20.5%, p = 0.026). The prevalence of nonviral HCC increased significantly from 19.2 to 19.3% and 23.0% in the last 10 years (p = 0.046). Overall survival was better in the viral HCC group (5.95 years versus 4.00 years, p < 0.001). In the early stage of HCC, overall survival was still better in the viral HCC group (p < 0.001). The prevalence of nonviral HCC has significantly increased in the last ten years. The overall survival was significantly lower in the nonviral HCC, perhaps because the rate of early HCC detection is lower in nonviral HCC and anti-viral therapy. To detect nonviral HCC early, we should evaluate liver fibrosis in high-risk groups (including people with obesity or T2DM with NAFLD/NASH and alcoholic liver disease) and regular follow-up for those with liver fibrosis, regardless of cirrhosis.

Hepatitis C Virus Genotypes and Viral Concentrations in Participants of a General Population Survey in the United States

The article presents a new method of intensification of antiviral therapy for chronic hepatitis B with intradermal autoleukocyte immunization during treatment with a drug of nucleotide analogues - tenofovir (patent UA 113873 U, 2017); other curative vaccines for chronic hepatitis B are also regarded. The research involves patients with chronic hepatitis B (30), whose replication of HBV DNA decreased to a certain level after long-lasting (over 2 years) antiviral therapy, its further reduction ceased. These patients underwent intradermal autoleukocyte immunization for intensification of antiviral therapy. Leukocytes were isolated from plasma of a patient's heparinized venous blood by centrifuging at 400 g for 8 minutes, after that the precipitate was resuspended in 1-1.5 ml of own blood serum and injected intradermally into the back in the dose 0.1 ml. Immunization was conducted at least 3 times with 30-40-day interval. Due to autoleukocyte immunization, the process of further decrease in virus reproduction resumed in 24 patients (out of 30; 80%). Out of six other patients (20%), in whom HBV DNA was detected only by supersensitive PCR method (sensitivity to 5 IU/ml) after long-lasting antiviral therapy, a negative result on examination was achieved in 2 individuals (33.33%). Autoleukocyte immunization intensifies efficiency of antiviral therapy for chronic hepatitis B with a drug from the group of nucleotide analogues.

Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients

Social support and clinical outcomes during antiviral therapy for chronic hepatitis C