Prevalence of occult HBV infection in haemodialysis patients with chronic HCV

AIM： To study the prevalence and clinical effects of occult HBV infection in haemodialysis patients with chronic HCV.METHODS： Fifty chronic hemodialysis patients with negative HbsAg, and positive anti-HCV were included in the study. These patients were divided into two groups： HCV-RNA positive and HCV-RNA negative, based on the results of HCV-RNA PCR. HBV-DNA was studied using the PCR method in both groups.RESULTS： None of the 22 HCV-RNA positive patients and 28 HCV-RNA negative patients revealed HBV-DNA in serum by PCR method. The average age was 47.2±17.0 in the HCV-RNA positive group and 39.6±15.6 in the HCV-RNA negative group.CONCLUSION： The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity （8%-10%） and frequency of HBV mutants in our region.

Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

Hepatitis C virus(HCV) infection is one of the mostfrequent causes of comorbidity and mortality in the human immunodeficiency virus(HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals(DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa(Peg-IFN) + ribavirin(RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCVgenotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence.

Progression of Platelet Counts in Treatment Naïve HIV/HCV Co-Infection

Background: Previous research has suggested an association between infection with hepatitis C virus (HCV) or with human immunodeficiency virus (HIV) and low platelet counts. This study estimates platelet count changes over time in HIV/HCV co-infected participants and compares them with the changes in platelet count among HIV mono-infected participants to test if HIV/HCV co-infection is associated with lower platelet counts. Methods: This retrospective cohort study included all HIV treatment naive patients from four sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort with platelet count measurements between 2002 and 2009. We conducted a mixed effects linear regression modeling the mean change in platelet count per year while adjusting for age, sex, race, baseline CD4 cell count, and site. Index date was the first platelet count after 2002, and participants were censored upon initiation of treatment for HIV or HCV. Results: There were 929 HIV/HCV co-infected and 3558 HIV mono-infected participants with a mean follow-up time of 1.2 years. HIV/HCV co-infected participants had on average a slighter lower platelet count at baseline (234,040 vs. 242,780/μL;p-value = 0.004), and a more rapid mean reduction per year (7230 vs. 3580/μL;p-value 0.001) after adjusting for age, sex, baseline CD4 count. Conclusions: In treatment naive participants, HIV/HCV co-infection is associated with a more rapid decline in platelet count compared with HIV mono-infection.

HBV and HCV infection and pancreatic ductal adenocarcinoma

Introduction Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy,with a poor overall fiveyear survival.Its dismal prognosis,even after curative resection,depends on its advanced stage at diagnosis,early metastatic spread,aggressive biological behavior and inefficacy of available systemic therapies.[1]To date,epidemiological studies have identified some risk factors for this cancer,including cigarette smoking habit,family history as well as high dietary fat consumption,alcohol abuse,diabetes mellitus,metabolic syndrome and chronic pancreatitis history.[1]

A Preliminary Study on the HCV Infection Status of Patients with Hemophilia and Their Family Members

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Effect of Time Delay and Antibodies on HCV Dynamics with Cure Rate and Two Routes of Infection

In this paper we propose and analyze an HCV dynamics model taking into consideration the cure of infected hepatocytes and antibody immune response. We incorporate both virus-to-cell and cell-to-cell transmissions into the model. We incorporate a distributed-time delay to describe the time between the HCV or infected cell contacts an uninfected hepatocyte and the emission of new active HCV. We show that the solutions of the proposed model are nonnegative and ultimately bounded. We derive two threshold parameters which fully determine the existence and stability of the three steady states of the model. Using Lyapunov functionals, we established the global stability of the steady states. The theoretical results are confirmed by numerical simulations.

Comparison between FIB-4 Index and Fibroscan as Marker of Fibrosis in Chronic HCV Infection in Egyptian Patients

The FIB-4 index is a simple and noninvasive algorithm consisting to evaluate liver fibrosis in chronic HCV infection. Aim: To evaluate the utility of FIB-4 index as a noninvasive marker to assess liver fibrosis in chronic HCV infection in comparison to transient elastography. Patients and Methods: We studied 30 patients having chronic HCV infection based on clinical features, laboratory tests, diagnostics images, Fibroscan and FIB-4 score. According to the results of Fibroscan, the 30 patients were classified into two groups in order to obtain a cutoff value to exclude patient with significant fibrosis: group Ia: 7 patients with no or mild liver fibrosis (F0-F1) and group Ib: 23 pa-tients with significant fibrosis or cirrhosis (F2-F3-F4). Group IIa: 17 patients with no or significant fibrosis (F0-F1-F2-F3) and group IIb (F4): 13 patients with cirrhosis (F4). Results: The mean of FIB-4 index increased with the increase of the fibrosis score. FIB-4 index proved to be sensitive and specific in differentiation between patients with no or mild fibrosis (F0-F1) and patients with significant fibrosis or cirrhosis (F2-F3-F4) with the best cutoff value at 1.61. It also proved to be sensitive and specific in differentiation between patients with no or significant fibrosis (F0-F1-F2-F3) and patients with cirrhosis (F4) with cutoff value at 1.88. Conclusion: The FIB-4 index enabled the correct identification of extreme types of fibrosis. Using these cutoffs (1.61 - 1.88), 87% of patients fell outside these ranges and could thus avoid liverbiopsy with an overall accuracy of 70%.

HIV/HCV Co-Infection—A Dual Neurocognitive Problem

Presence of the hepatitis C virus in HIV infected patients has an additional neurotoxic influence on the Central Nervous System. It has been described that HCV co-infection leads to neuropsychological impairment whose severity is greater than in mono-HIV infected subjects. In the present study we assessed the neuropsychological status of 46 human immunodeficiency virus (HIV)-infected individuals from the Warsaw Hospital for Infectious Diseases. For the purpose of cognitive assessment, neuropsychological tests measuring global cognitive functions, attention and perception, verbal memory, as well as non-verbal aspects of executive functions, e.g. visual monitoring and planning, were assessed. In 60% of the investigated patients, who were co-infected with the hepatitis C virus, the overall cognitive outcome observed was worse than in mono-HIV infected subjects. The following factors were taken into account: ART therapy’s influence on cognitive functions using the CPE rank (CNS Penetration Efficacy, 2010), route of HIV transmission, conditions of human existence and age of investigated patients. The present work should be treated as a preliminary research and interpreted in the context of several limitations described in the text.

Antiretroviral Therapy in HIV/HCV Co-Infection Italian Consensus Workshop

About 50% of people living with the HIV infection in Italy are co-infected with HCV. In this group of patients, the primary cause of mortality is liver disease, which accounts for up to 14% of deaths. HIV/HCV co-infection also exposes patients to a higher risk of progression to AIDS, a faster evolution towards cirrhosis, more frequent drug toxicity, and lower tolerance for antiretroviral therapy. Moreover, HCV infection can play a part in increasing immune system depression;neurological, cognitive and renal damage;and bone fragility. Hence an optimal antiretroviral regimen needs to be chosen for co-administration with anti-HCV therapy and timed appropriately to improve the prognosis of co-infected HIV/HCV patients. Unfortunately, however, data on the safety and efficacy of antiretroviral drugs in these patients is scarce, as are studies of pharmacokinetics in patients with advanced liver impairment. Furthermore, restoring adequate immune constitution seems not to slow the progression of liver disease, and the metabolic and hepatic toxicity of some antiretroviral drugs can even contribute to inflammatory and fibrogenic processes. It is therefore essential that HIV/HCV co-infected patients receive only medications capable of ensuring the best immune recovery but possessing the lowest potential to trigger immune reconstitution syndrome or hepatic and metabolic damage.

Stratification of the Degree of Hepatic Involvement in HIV-HCV Coinfection Using Two Biomarkers: APRI and FIB-4

Hepatitis C infection in people living with Human Immunodeficiency Virus (HIV) poses management challenges. Of the world’s population, 3% are estimated to have chronic Hepatitis C Virus (HCV) infection, which is responsible for about 70% of cases of chronic hepatitis (accelerated chronicity in the presence of HIV and for such major complications as cirrhosis and hepatocellular carcinoma. The fibrosis 4 (FIB-4) and Aspartate aminotransferase/platelet ratio index (APRI) scores are simple, inexpensive tests accessible to most people, and their performance has not yet been studied in C?te d’Ivoire. Objective: To prospectively evaluate the diagnostic performance of APRI and FIB-4 scores in liver damage in those co-infected with HIV/HCV in C?te d’Ivoire. Methods: This study was conducted over three months. The patients came from national blood transfusion center of the cities of Man and Daloa. The criteria for selecting respondents were at least 18 years of age and a positive test for HIV and HCV. APRI and FIB-4 scores were calculated for each patient from biological data obtained by COBAS C311 (Roche Hitachi, Japan). Statistical analyses were performed using GraphPad and MED-CALC software. Results: Our study involved 30 patients (men) of middle age (25 - 52 years), with extremes ranging from 0.67 to 8 for APRI and 0.201 to 22 for FIB-4. A predictive APRI and FIB4 score of significant hepatic fibrosis was observed in 23% of patients;however, 46% and 54% of patients for the APRI and FIB-4 score, respectively, would not have significant fibrosis. An APRI and FIB4 score not included in the classification limits of the type of fibrosis hepatitis was observed in 31% and 23% of patients, respectively. Conclusion: The performance of the APRI and FIB-4 biological scores analyzed according to the interpretation of their cut-off values would enable classifying about 70% and 77%, respectively, of the patient population in the stages of hepatitis C fibrosis.

The Impact of Human Parvovirus B19 Co-Infection on Liver Function of HCV Infected Patients

Background: Human Parvovirus B19 is most known for causing disease in the pediatric population but can also affect adults. Human co-infection with Parvovirus B19 could deteriorate the prognosis of patient with chronic ill-ness. Objectives: This paper attempts to determine the prevalence of Parvovirus B19 in HCV infected patients and to evaluate the impact of Parvovirus B19 on liver enzymes activity of Hepatitis C patients. Study Design: The study population includes 74 chronic HCV (patient group) and 49 cases without viral hepatitis (control group). Nucleic acid of Parvovirus B19 was detected in Serum samples by nested polymerase chain reaction (nested-PCR) method. Results: Parvovirus B19-DNA infection was detected in 28.0% of chronic HCV patients. Parvovirus B19-HCV co-infection caused increasing in Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) activity than in B19-negative HCV patients. Conclusion: We conclude that Parvovirus B19 acted synergistically with HCV by increasing the levels alanine ami-notransferase (ALT) and Aspartate aminotransferase (AST).

Hepatitis C virus infections and genotypes in China

Objective: To define the conditions of hepatitis C vi- rus (HCV) infections, and geographic and demo- graphic distributions of genotypes in China. Methods: HCV infected patients were selected from individuals with different patterns of liver diseases and high risk populations in different parts of China. Genotypes of HCV in some isolates were further ana- lyzed, based on the data from our laboratory studies and some carefully selected published literatures. Results: The anti-HCV positive rates were 9.7% in patients with acute hepatitis, 13.3% in patients with chronic hepatitis, 18.3% in patients with hepatocel- lular carcinoma, 33.0% in patients with liver cirrho- sis, and 43.2% in patients with posttransfusional hepatitis (average, 16.2% in patients with liver di- seases). The anti-HCV positive rates in the high risk populations were 36.4% in leukemic patients, 43.0% in hemodialysis patients, 12.7% in blood do- nors, 64.1% in drug abusers, 13.1% in prostitutes, and 2.57% in naturally healthy people. At least 4 clades (clades 1, 2, 3 and 6) of HCV were found in China with different geographic and demographic distributions. Genotype 1b was the most widely dis- tributed genotype, and genotype 3 was mainly found in Yunnan Province, Southwest China. Conclusion: China has a high incidence of HCV in- fection. Our results will provide a strategic basis for diagnosis, treatment and possibly prophylaxis of he- patitis C virus diseases.

Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection: A pilot study

AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients. METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs. RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy. CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- a may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.

Efficacy and Safety of Glecaprevir/Pibrentasvir in Combination Therapy in Chronic Hemodialysis Patients with Genotype 2 Hepatitis C Virus Infection

Background: Glecaprevir (nonstructural protein 3/4A protease inhibitor) and Pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-antiviral regimen, was evaluated for safety and efficacy in chronic hemodialysis patients with genotype 2 hepatitis C virus infection. Methods: In this prospective, observational, single-center study at Masuko Memorial Hospital, between November 2017 and December 2018, a total of 8 HD patients with an HCV infection genotype 2 received G/P combination therapy. Age was an average of 67.1 (61 - 75) years and there were four men and two women. It was FIB4 INDX an average of 2.67 (1.5 - 3.34) before the start of therapy. It was quantity of HCV RNA an average of 4.43 (2.1 - 6.5). HCV RNA levels were measured by real-time RCR-based method (COBAS AmpiPrep/COBAS TaqMan HCV Test. 4 cases 12 weeks were 2 cases eight weeks for dosing period. Patients were excluded if they had evidence of hepatocellular carcinoma. This study was approved by the ethics committee of our hospital, while we obtained written consent from the participants after providing a thorough explanation of the contents and methods of this study. Results: 6 patients were available for total dose internal use. As for the HCV RNA of the fourth week, (100%) HCV RNA became negative after administration start of therapy. Rapid virologic response (RVR) achieved all cases. 5 patients achieved 12-week sustained virologic response (SVR12) and were following up the 1 patient. The itching appeared in two cases (33%), but there was symptom improvement in nalfurafine hydrochloride use treatment, and treatment continuation was possible. Conclusion: It is thought that G/P can be given to the HD patients’ safety, but we will accumulate a case in future, and it is thought to be necessary to examine utility and safety.

Long term immunological perturbations post DAA therapy in chronic HCV/HIV co-infected patients

Direct-acting antiviral(DAA)therapies are efficacious for the achievement of sustained virologic response(SVR)in almost all treated hepatitis C virus(HCV)-infected patients.However,the impacts of HCV eradication on immune function and chronic immune activation in the long-term remain controversial and limited,especially in patients co-infected with human immunodeficiency virus(HIV).Indeed,although restoration of many immune responses clearly can be observed,several features of immune perturbations persist over time after HCV clearance.Understanding the degree and reasons of the partial recovery of the immune system in chronic HCV/HIV coinfection after HCV elimination is pivotal to avoid disease progression and possible long-term clinical outcomes in cured patients,as well as contributing to the development of immunotherapy drug design.

Exosomes in viral infection:Effects for pathogenesis and treatment strategies

Exosomes are small vesicles that carry molecules from one cell to another.They have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and selective delivery.Exosomes can also interact with viruses in diverse ways.Emerging research highlights the significant role of exosomes in viral infections,particularly in the context of diseases like COVID-19,HIV,HBV and HCV.Understanding the intricate interplay between exosomes and the human immune system holds great promise for the development of effective antiviral therapies.An important aspect is gaining clarity on how exosomes influence the immune system and enhance viral infectivity through their inherent characteristics.By leveraging the innate properties of exosomes,viruses exploit the machinery involved in exosome biogenesis to set replication,facilitate the spread of infection,and eliminate immune responses.They can either help or hinder viral infection by modulating the immune system.This review summarizes the recent findings on how exosomes mediate viral infection and how they can be used for diagnosis or therapy.This could lead to new clinical applications of exosomes in disease management.

Mathematical Analysis of Control Strategies of HCV in a Community with Inflow of Infected Immigrants

In this paper, we derive and analyse rigorously a mathematical model of control strategies (screening, education, health care and immunization) of HCV in a community with inflow of infected immigrants. Both qualitative and quantitative analysis of the model is performed with respect to stability of the disease free and endemic equilibria. The results show that the disease free equilibrium is locally stable at threshold parameter less than unity and unstable at threshold parameter greater than unity. Using Lyapunov method, endemic equilibrium is globally stable under certain conditions. Numerical simulation of the model is implemented to investigate the sensitivity of certain key parameters on the HCV model in a community with inflow of infected immigrants. However, analysis shows that screening, education, health care and immunization have the effect of reducing the transmission of the disease in the community.