Serum HCV-RNA Levels Research Articles

Hospital-based screening outperforms primary care screening as a means of achieving hepatitis C virus micro-elimination

AimTo assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. MethodsAdult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. ResultsSeroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. ConclusionsHospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.

ABCA1 Polymorphism R1587K in Chronic Hepatitis C Is Gender-Specific and Modulates Liver Disease Severity through Its Influence on Cholesterol Metabolism and Liver Function: A Preliminary Study.

Chronic hepatitis C (CHC) progression is highly variable and can be influenced by lipid metabolism. The ATP-binding cassette transporter A1 (ABCA1) is involved in lipid metabolism and mediates cholesterol efflux from liver cells. ABCA1 gene polymorphism rs2230808 (R1587K) modulates lipid levels as it is located in an ABCA1 protein domain, which is essential for cholesterol efflux. We aimed to analyze the role of ABCA1 polymorphism R1587K (rs2230808) in modulating the biochemical parameters of lipid metabolism and liver function and its association with liver disease severity, according to gender. A total of 161 CHC patients were clinically, histologically, and biochemically evaluated. Genotyping was performed by melting-curve analysis and statistical analysis by SPSS 24.0. There were significant differences between ABCA1_rs2230808 genotypes and total cholesterol, γGT (γ-glutamyl-transpeptidase), and HCV-RNA. Gender differences: in females, ABCA1_rs2230808 (GG or GA) was associated with higher HCV-RNA serum levels; in males, ABCA1_rs2230808 (GG or GA) was associated with higher γGT, lower total cholesterol, increased risk for γGT ≥ 38 UI/L, and total cholesterol < 4.92 mmol/L. Only in the case of males were higher γGT and lower total cholesterol associated with severe fibrosis and steatosis. Total cholesterol < 4.92 mmol/L also associates with severe necroinflammation. We conclude that ABCA1_rs2230808 is gender-specific. ABCA1_rs2230808 Allele G was associated with different clinical and biochemical parameters, which are related to more severe liver disease.

Distribution of chronic hepatitis C genotype and evaluation of clinical factors affecting direct-acting antiviral treatment responses in the Western Black Sea Region, Turkey.

Chronic Hepatitis C (CHC) is a substantial global public health issue with significant variation between countries because of the genotypic differences. A sustained viral response (SVR) is essential to reduce the complications associated with CHC and can be achieved in most patients via direct-acting antivirals (DAAs). The present study aimed at determining the genotype distribution in patients with CHC in our region and the SVR in DAA therapy patients. The study was conducted retrospectively on 272 patients treated with DAA between September 2016 and 2021. Data including demographic and clinical characteristics of the patients (HCV RNA level, genotype, hepatitis B and HIV serology, cirrhosis and decompensation, presence of hepatocellular cancer, degree of hepatosteatosis, previous anti-HCV treatment experience, comorbidities) were recorded. The study's primary endpoint was to determine the SVR at week 24. Genotype 1 was the most common genotype (94.5%), with genotype 1b accounting for most patients (78%) among those. It was observed that the patients received Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir (OPRD) (47%), Ledipasvir/sofosbuvir (LDS) (38%), and Glecaprevir/pibrentasvir (GCP) (15%) as DAA treatment. SVR was observed in 92% (223) of the 240 patients at the end of 24 weeks. SVR-24 was significantly higher in the patient group with serum HCV RNA level ≤ 852.533 (p=0.002), in the hypertensive group (p=0.018), and without the psychiatric disease group (p<0.001). A high rate of SVR-24 was achieved by DAAs in CHC patients, most of whom were genotype 1 in the Western Black Sea Region, Turkey. Also, high viral load, hypertension, and psychiatric disease affected SVR-24, and clinical factors, such as cirrhosis, cirrhosis complications, hepatosteatosis, and other comorbidities did not.

A Multicenter Controlled, Randomized, Open Trial of Interferon α2b Treatment of Anti–Human Immunodeficiency Virus-Negative Hemophilic Patients With Chronic Hepatitis C

AbstractThere is limited information about the long-term efficacy of prolonged therapy (more than 6 months) with interferon α in hemophilic patients with chronic hepatitis C who are not coinfected with the human immunodeficiency virus (HIV-1). One hundred and seven hemophiliacs were randomly assigned to 3 million U of interferon α2b three times weekly for 12 months or no therapy. The patients were followed up for at least 12 months posttreatment. Response was assessed by both serial alanine aminotransferase (ALT) levels and hepatitis C virus (HCV)-RNA measured by reverse transcribed polymerase chain reaction (RT-PCR) method. Before treatment, serum levels of HCV-RNA were measured quantitatively by second-generation branched-DNA assay and the HCV genotype was determined by RT-PCR. Serum HGV-RNA, a marker of infection with the hepatitis G virus, was also measured by RT-PCR. Normalization of ALT was sustained and serum HCV-RNA was cleared in 6 of 45 treated patients, compared with none of the 50 untreated controls (13% v 0% P < .01). Low pretreatment viremia was the only feature that was associated with an increased likelihood of sustained response (P < .01). This study shows that multitransfused hemophiliacs with chronic hepatitis C not coinfected with HIV-1 respond at low rates to prolonged interferon therapy.

Multicenter clinical evaluation of alinity m HCV assay performance.

Nucleic acid testing is essential for the detection and quantification of HCV RNA in the diagnosis of HCV infection and treatment monitoring. The Alinity m HCV assay was recently developed by Abbott Molecular for rapid detection and quantification of HCV RNA on the fully automated, continuous, random-access Alinity m analyzer. Our study assessed the performance of the new Alinity m HCV assay for detection and quantification of HCV RNA in a large series of patient samples of various genotypes. This international, multicentric study evaluated the linearity, precision, and reproducibility of the Alinity m HCV assay and its performance in comparison to three other HCV assays currently used in clinical practice. The Alinity m HCV assay demonstrated high linearity (correlation coefficient r = 1.00), precision (coefficients of variation [CV] 6.6-13.5 %) and reproducibility (CV 1.7-4.3 % across three control lots). At a concentration near the lower limit of detection, the Alinity m HCV assay exhibited >98 % detectability. The Alinity m HCV assay showed excellent correlation with comparator HCV assays in serum (n = 406) and plasma (n = 1401) samples (correlation coefficients ≥0.96, bias 0.01 to 0.14 Log10 IU/mL). More than 95 % of the quantified results with the Alinity m HCV assay were less than mean bias ± 1.96 SD different from those of the comparator assays. The newly developed Alinity m HCV assay is sensitive, reproducible, and accurately quantifies HCV RNA levels in serum and plasma samples from patients with chronic HCV infection, with no impact of HCV genotype on assay performance.

Changes of inflammatory cytokines/chemokines during ravidasvir plus ritonavir-boosted danoprevir and ribavirin therapy for patients with genotype 1b hepatitis C infection.

This study investigated the safety and efficacy of ravidasvir (RDV) plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimens for treatment-naïve non-cirrhotic patients with hepatitis C virus (HCV) genotype 1b in mainland China. We also gained insight into HCV-host interactions during anti-HCV treatment. 16patients with HCV and 10 healthy people enrolled the study. Threeof 16 patients received 12-weeks' placebo treatment first and served as the placebo controls. All (n = 16) patients received 12-weeks' RDV plus DNVr and RBV treatment. The adverse effects (AEs), viral loads, alanine transaminase,and aspartate aminotransferasewere recorded during study. We also performed multianalyte profiling of 48 cytokines/chemokines in 16 patients with HCV and 10 normal controls. Seventy-five percent patients treated with RDV plus DNVr and RBV experienced AEs. No death, treatment-related serious AEs or AEs leading to discontinuation were reported. The serum HCV-RNA levels remained extremely high in 3placebo controls after treated with placebo. After RDV plus DNVr and RBV treatment, all patients achieved sustained virologic response (SVR) at posttreatment week 12, but 1patient experienced viral relapse at SVR 24. The cytokine/chemokine expression pattern was markedly altered in patients with HCV as compared withhealthy controls. The interferon-inducible protein-10 (IP-10) decreased after anti-HCV treatment, and dramatically increased in one patient with viral relapse. The regimen of RDV and DNVr plus RBV represents a highly safe and effective treatment option for HCV patients in mainland China. The IP-10 has the potential to be an indicator of innate immune viral recognition.

2278 Rapidly Progressive Hepatitis C After Liver Transplantation Treated With Glecaprevir/Pibrentasvir

INTRODUCTION: Hepatitis C recurrence following liver transplantation occurs in all patients with chronic HCV infection who have detectable serum HCV RNA levels prior to transplant. Less than 10% of these patients develop an acute and severe phenotype called fibrosing cholestatic hepatitis, which often involves fibrosis, rapid graft loss and decreased survival. The introduction of direct-acting antiviral agents (DAAs) have changed the paradigm of treatment of these patients. CASE DESCRIPTION/METHODS: A 62-year-old woman with a medical history of hepatitis C infection, hepatocellular carcinoma status post orthotropic liver transplantation, diabetes mellitus and hypertension who was hospitalized for fatigue and elevated liver chemistries following her liver transplantation. Laboratory tests showed a white cell count 6.67 × 103/μL, creatinine 1.1 mg/dL, aspartate aminotransferase 592 U/L, alanine aminotransferase 504U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL, albumin 2.9 g/dL. Acute hepatitis work up showed a positive hepatitis C virus antibodies with genotype 1B, with a viral load of 80 million IU/mL HCV RNA. HBsAg, HBc IgG, HBc IgM, and hepatitis A virus IgM were negative. Evaluation for Epstein-Barr virus, cytomegalovirus and herpes simplex virus were negative. Ultrasound of the abdomen revealed that the liver is normal in size, echotexture and contours. No focal hepatic lesions. Normal hepatic blood flow. The patient underwent liver biopsy that showed lymphocytic portal inflammation with frequent lobular apoptosis consistent with active chronic hepatitis C (MHAI: 5-6/18). Mild portal fibrosis (ISHAK FIBROSIS STAGE: 1/6) and minimal evidence of acute t cell-mediated rejection (rejection activity index: 1/9). During the patient hospitalization her liver chemistries significantly worsened and peaked to aspartate aminotransferase 740 U/L, alanine aminotransferase 511U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL. We decided to start the patient on Glecaprevir/Pibrentasvir for acute and severe hepatitis. Fourteen days after starting Glecaprevir/Pibrentasvir, the patient viral load decreased to 782 IU/mL HCV RNA and normalized liver chemistries with AST19 and ALT 27. The patient denied any adverse events due to the treatment. DISCUSSION: To our knowledge, this is the first case report of treating early and aggressive form of HCV recurrence with Glecaprevir/Pibrentasvir. The dramatic improvement of the patient suggest that DAA might be safe and effective in this situation.

Hepatitis C Virus RNA Is Commonly Detectable in Rectal and Nasal Fluids of Patients With High Viremia.

Increasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex practices and associated drug use remain poorly understood. Forty-seven patients with HCV were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was excluded by guaiac paper test. Risk behavior was assessed by standardized questionnaires. Median age was 41.9 years, 89% were HIV positive (+) (42/47) and 85% (40/47) were male, 58% (23/40) of whom were MSM. Acute HCV infection was diagnosed in 32% (15/47) ,with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had ≥1 HCV+ swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal), and contamination with blood was excluded in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 [IQR, 0.85] log IU/mL vs 4.08 [2.45] log IU/mL; P < .001). Using ROC-curve analysis, serum HCV-RNA cutoffs for ruling in/out any HCV+SS were established at 6.02 log IU/mL and 4.02 log IU/mL, respectively. HCV-RNA is commonly detectable in rectal and nasal fluids of both HIV+ and HIV-negative HCV patients with high serum HCV-RNA, independently of the suspected route of HCV transmission. Accordingly, high-risk sex practices and sharing of nasal drug-sniffing "tools" might be important HCV transmission routes, especially in patients with high serum HCV-RNA.

The impact of hepatitis C viremia status on lung functions in chronic hepatitis c patients.

Previous trials have investigated the effect of hepatitis C on lung functions; however, the role of viral load levels is unclear. The aim of this study was to investigate the effect of HCV viremia status on lung functions. This study was in 60 patients with chronic hepatitis C (CHC). Patients were classified into three groups (non-viremic, low-viremic and high-viremic) based on serum HCV RNA levels. Spirometric parameters (FEV1, FVC, FEV1/FVC) and the proportion of patients with spirometric abnormalities were compared between three groups. High-viremic and low-viremic patients showed a significantly higher prevalance of spirometric abnormality than observed in non-viremic patients (p=0.02). Moreover, there was a significant moderate correlation between viremia level and the percentage of spirometric abnormalities (Cramer's U value=0.452, p=0.002). High-viremic patients were 14.2 times more likely to exhibiting pulmonary dysfunction than non-viremic patients. Additionally, spirometric parameters FEV1 and FVC were significantly reduced in high-viremic and low-viremic patients compared to those in non-viremic patients (p=0.013 and p<0.001 respectively). These results indicate that persistent HCV infection may be associated with reduced pulmonary functions, especially in patients with high viremia levels. Therefore, these patients should be carefully monitored for lung function.

Confirmation of HCV viremia using HCV RNA and core antigen testing on dried blood spot in HIV infected peoples who inject drugs in Vietnam

BackgroundNucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam.MethodOne hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study).ResultsEighty-six subjects were tested positive for HCV RNA in serum, median (IQR): 6.9 log10 IU/ml (5.6–7.4 log10 IU/ml). Genotypes consisted of 57 G1 (69%), 3 G3 (4%), and 22 G6 (27%). HCV RNA was detected on DBS specimens in 79 out 86 subjects with chronic hepatitis C (sensitivity 92.5%; 95% CI: 85.1–96.9%). HCV RNA level on DBS and serum was moderately correlated (r = 0.24; p = 0.05) suggesting a degradation of HCV RNA due to transportation and storage conditions. HCVcAg was detected in 75/86 dB specimens (sensitivity: 87.2%; 95% CI: 78.3–93.4%), with a strong positive relationship between DBS HCVcAg and serum HCV RNA levels (r = 0.80; P < 0.0001).ConclusionsQuantification of HCVcAg on DBS appears to benefit from substantial stability under prolonged storage conditions but with a lower analytical sensitivity compared to DBS HCV RNA testing. Detection of HCV RNA on DBS is an interesting approach for confirming viral replication in HCV seropositive persons but the impact of pre-analytical conditions on the integrity of HCV RNA needs to be controlled.

Significance of day-1 viral response of hepatitis C virus in patients with chronic hepatitis C receiving direct-acting antiviral therapy.

On-treatment response of serum hepatitis C virus (HCV) is reportedly less useful to predict the outcome of anti-HCV therapy with interferon (IFN)-free regimen with direct-acting antivirals than with IFN-based regimens in clinical trials. We evaluated the significance of very early viral response after the start of therapy, which indicates direct HCV response to the drugs, on therapeutic outcome. Reductions in serum HCV-RNA levels were measured at 1day after the start of therapy in 544 patients who underwent IFN-free direct-acting antiviral regimens. The association between these reductions and the achievement or failure of sustained virologic response (SVR) was evaluated. Patient characteristics did not influence 1-day reduction in serum HCV-RNA except for liver fibrosis. There was no difference in 1-day HCV reduction between SVR and non-SVR patients treated with a 24-week regimen. In contrast, in patients treated with a 12-week regimen, 1-day reduction was significantly greater in SVR than in non-SVR patients (P=0.0013) and was predictive of SVR versus non-SVR (area under the receiver-operating characteristics curve: 0.80). Whereas the reduction in serum HCV-RNA levels at 1day after the start of therapy was not associated with treatment outcomes in patients who underwent a 24-week regimen of IFN-free therapy, there was an association in patients receiving a 12-week regimen, and this reduction was predictive of SVR, thus potentially serving as a factor to identify patients at risk of treatment failure.

Real‐world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for patients with chronic hepatitis C virus genotype 1b infection in Taiwan

The real-world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) remain limited for East Asian hepatitis C virus genotype 1b (HCV-1b) patients. The study aimed to evaluate the antiviral responses of PrOD-based regimens for HCV-1b patients in Taiwan. The study performed a retrospective analysis of 103 HCV-1b patients receiving PrOD with or without ribavirin (RBV) for 12weeks. Data were analyzed to assess the on-treatment and off-therapy HCV viral load and on-treatment adverse events. The pre-specified characteristics related to sustained virologic response 12weeks off therapy (SVR12 ) were compared. At treatment week 4, 100 of 102 patients (98.0%) had serum HCV RNA level <25IU/mL. The SVR12 was achieved in 101 of 103 patients (98.1%, [95% confidence interval: 93.2-99.5%]). All except one (99.0%) patients tolerated treatment well without treatment interruption. One cirrhotic patient discontinued treatment at week 1 due to hepatic decompensation. Twenty-four patients (23.3%) had ≥ grade 2 elevation in total bilirubin levels, and 21 of them (87.5%) had indirect type hyperbilirubinemia. The stratified SVR12 rates were comparable in terms of sex, age, body mass index, prior treatment experience, hepatitis B virus surface antigen status, RBV usage, baseline and week 2 viral load, renal function, and hepatic fibrosis stage. Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without RBV are efficacious and generally well tolerated for treatment of HCV-1b patients in Taiwan.

Disappearance of perihepatic lymph node enlargement after hepatitis C viral eradication with direct-acting antivirals.

Perihepatic lymph node enlargement (PLNE) which has been shown to be negatively associated with hepatocellular carcinoma (HCC) occurrence is frequently observed in chronic liver disease; however, changes in the state of perihepatic lymph nodes after eradication of hepatitis C virus (HCV) have not been investigated yet. We aimed to evaluate this issue. We enrolled 472 patients with chronic HCV infection who achieved viral eradication with direct-acting antivirals (DAA). We investigated whether the status of perihepatic lymph nodes changed before and after HCV eradication (primary endpoint). We also evaluated the association between PLNE and clinical findings such as liver fibrosis or hepatocellular injury before HCV eradication (secondary endpoint). Perihepatic lymph node enlargement was detected in 164 of 472 (34.7%) patients before DAA treatment. Surprisingly, disappearance of PLNE was observed in 23.8% (39 patients) of all PLNE-positive patients after eradication of HCV. Disappearance of PLNE was not associated with baseline clinical parameters or changing rates of clinical findings before and after DAA treatment. At baseline, presence of PLNE was significantly associated with a lower serum HCV-RNA level (P=.03), a higher serum AST level (P=.004) and a higher ALT level (P<.001) after adjustment for sex and age. In conclusion, PLNEs became undetectable after DAA treatment in 23.8% of PLNE-positive patients. Further study with a longer follow-up period is needed to clarify the clinical importance of this phenomenon especially in relationship with the risk of HCC development.

Correlation between hepatitis C viral load and hepatitis C Core antigenaemia among Egyptians.

Hepatitis C virus (HCV) infection is widespread in Egypt. This study compared HCV RNA with HCVcAg for the detection and quantification of viraemia among a sample of Egyptians. Sera from 80 suspected HCVpositive individuals were tested simultaneously for HCV-RNA load using real-time polymerase chain reaction (PCR) and HCVcAg level using ELISA. Of the 80 samples, 25% were HCV-RNA-negative. HCVcAg was detected in all samples: range 0.4-2462 ng/mL, mean 460 (SD 506) ng/mL. The sensitivity and specificity of HCVcAg were 96.7% and 90.9%, respectively. There was a significant correlation between serum HCV-RNA and HCVcAg levels (r = 0.4, P < 0.0001). HCV-RNA remains the gold standard for diagnosis of active HCV infection but HCVcAg can be used where PCR is not available.

Chronic Hepatitis B Reactivation Subsequent to Chronic Hepatitis C Treatment: A Case Report

Patients, who are coinfected with hepatitis B and C, are at high risk for a progression to severe liver disease (cirrhosis, decompensated liver disease), hepatocellular carcinoma, and unresponsiveness to treatment. In this article, a case who developed a reactivation of chronic hepatitis B subsequent to Chronic Hepatitis C (CHC) treatment is presented. A 42-year-old woman with HBV and HCV was admitted to infectious diseases clinic with a major complaint of fatigue for three months. Laboratory tests revealed an elevated alanine transaminase of 182 IU/L (Normal range: 0-55 IU/L), elevated aspartate transaminase of 150 IU/L, serum HCV-RNA levels of 2080195 IU/mL (genotype 1b), and HBV-DNA of 1184 IU/mL. The results of other laboratory tests were within the normal range and remained to be normal during the follow-up. Pegylated interferon alpha-2a (180 mcg/week) and ribavirin (1200 mg/day) were administered for the treatment of CHC for 48 weeks. After one year of CHC treatment, our case was admitted with the elevation in liver enzymes and HBV-DNA of 878215 IU/mL. The histopathological examination of liver tissue revealed a mildly active histologic activity (6/18) and a mildly active histological activity (1/6) according to ISHAK scoring. Tenofovir disoproxil tablet (245 mg/day) was initiated for the chronic hepatitis B treatment. The patient is followed up at the ambulatory clinic of infectious diseases. As a result, patients coinfected with HBV and HCV should be followed up for the reactivation of HBV after CHC treatment with either pegylated interferon-based therapy or oral direct-acting antiviral agents in the medium-term, and the cirrhosis and hepatocellular carcinoma in the long-term.

Clinical efficacy of Rong-Yang-Jyh-Gan-Tang on patients with chronic hepatitis C: A double-blinded randomized placebo-controlled crossover study

Ethnopharmacological relevanceTraditional Chinese medicine (TCM) has been widely used by the Chinese population for treatment of chronic hepatitis. However, the efficacy of TCM for patients with chronic hepatitis has not been confirmed, mostly due to the lack of available scientific parameters such as serum viral load to evaluate treatment response. Aim of the studyWe evaluated the efficacy of Rong-Yang-Jyh-Gan-Tang (RYJGT, composed of Long-Dan-Xie-Gan-Tang, Jia-Wei-Xia-Yao-San, Dan-Shen, and Hou-Po) on patients with chronic hepatitis C. Materials and methodsThirty-six patients with chronic hepatitis C who had no response to or had contraindications to interferon-ribavirin therapy were randomly allocated to receive RYJGT 15g/day or placebo for 12 weeks. After a 2-week washout period, patients were crossed over to receive placebo or RYJGT for another 12 weeks. Evaluation parameters included liver biochemistries, serum HCVRNA, side effects of RYJGT/placebo, and TCM symptoms. ResultsOf the patients who had 12-week RYJGT treatment, 51.7% had decreased serum HCVRNA levels, whereas only 25.8% patients had decreased levels in the placebo group (p=0.036). TCM patterns of “Damp-Heat” and “Liver Qi Depression” had significantly improved after RYJGT treatment in comparison with the placebo. Logistic analyses showed that RYJGT treatment, and pre-treatment values of TCM symptoms of “Damp-Heat” and “Liver Qi Depression”, were statistically significant factors in predicting the decrease in serum HCVRNA. ConclusionChronic hepatitis C patients who received a 12-week RYJGT treatment had significantly higher HCVRNA decrease ratio, and improved TCM symptoms of “Damp-Heat” and “Liver Qi Depression”, than those who received the placebo. Our results require further larger scale clinical trials.

Platelets as a Possible Reservoir of HCV And Predictor of Response to Treatment

In the era of new Hepatitis C Virus (HCV) therapy, and the detection of extrahepatic HCV reservoirs such as peripheral blood mononuclear cells and platelets, it is important to understand the factors underlying resistance to treatment. Detection and quantitation of HCV-RNA in platelets or leucocytes from patients under antiviral therapy is poorly studied and the limited studies generated contradictory results. Aim: To detect and quantify HCV-RNA in platelets, and to evaluate the relation between HCV-RNA in the serum and the kinetics of HCV-RNA in platelets, in response to treatment. Method: Viral kinetic was tested in 20 chronic HCV genotype4, during the course of therapy. Results: HCV-RNA was detected in sera of all infected patients. The baseline platelet viral load was significantly lower in responders compared to non-responders. Platelet viral load was also related to serum viral load (t=3.39, p=0.001), but not related to platelet count (t=-0.56, p=0.58). ROC curve analysis revealed that in general, platelet viral load at different time points was a better predictor of SVR compared to serum viral load. Conclusion: HCV RNA analysis in whole blood may be more sensitive than platelet-poor plasma, which might underestimate circulating viral load. Early eradication of viremia from platelets is associated with higher rates of SVR. Our data, reconfirm higher HCV-RNA levels in serum compared to platelets. Thrombocytopenia occurring during interferon-based therapy might be a manifestation of viral eradication rather than adverse effects. Our findings warrant testing the sensitivity of platelet viral load as a predictor of poor response.

Prevalence of occult hepatitis C virus in patients with HCV-antibody positivity and serum HCV RNA negativity

Introduction and aim Chronic hepatitis C infection is a global problem with an increasing burden on healthcare, particularly in Egypt. Even with the advent of highly sensitive techniques, a subset of patients with positive hepatitis C virus antibody (HCV-Ab) and negative HCV-viremia remain challenging to treat. Therefore, we tried to determine the prevalence of occult HCV infection (OCI) in peripheral blood mononuclear cells (PBMCs) of patients presenting with a positive serologic test for anti-HCV-Ab and negative serum HCV-RNA-PCR (spontaneously cleared patients) and followed up those patients. Patients and methods Between March 2010 and March 2015, a prospective study was designed to include all consecutive patients with HCV-Ab positivity and HCV-RNA negativity who attended the Assiut Unit for treatment of viral hepatitis - the National Committee for Control of Viral Hepatitis. A total of 25 patients were recruited. Spontaneous clearance of serum HCV infection was approved on the basis of HCV-Ab positivity using two third-generation enzyme-linked immunosorbent assay tests and serum HCV RNA negativity on three consecutive occasions, each 6 months apart. Follow-up serum HCV RNA levels were evaluated for patients with OCI every 6 months. The RNA extraction step was performed by a protocol modified from that of the QIAamp viral RNA kits. Blood samples for separation of PBMCs were collected from all patients. PBMCs were obtained using Ficoll-Hypaque density gradient of EDTA anticoagulated blood according to the manufacturer's instructions (Lymphoflot). Detection of HCV viral load was performed with the kit supplied by Applied Biosystem (HCV RT-PCR Kit lot No.). Results A total of 25 patients (21 men, mean age 36.2 ± 9.1) cleared HCV spontaneously (HCV-Ab positive and serum HCV RNA negative). Genomic HCV RNA was detected in PBMCs of three (12%) of 25 patients. These three patients with OCI were followed up for 18 months by measuring their serum HCV RNA using highly sensitive real-time PCR every 6 months. Only one patient became overt HCV with a low level of viremia. Conclusion OCI was detected in a considerable prevalence in patients who cleared HCV spontaneously, that entails corporations of HCV-viral assay in PBMCs into the diagnostic algorithm.

Interaction between hepatic membrane type 1 matrix metalloproteinase and acireductone dioxygenase 1 regulates hepatitis C virus infection.

Membrane type 1 matrix metalloproteinase (MT1-MMP) binds to and regulates the function of tetraspanin-enriched microdomains. It also physically interacts with claudin-1 and acireductone dioxygenase 1 (ADI1), both associated with hepatitis C virus (HCV) cell entry. Here, we examined hepatic expression of MT1-MMP, ADI1 and claudin-1 as well as their physical interaction in relation to serum or intrahepatic HCV-RNA levels. A total of 104 liver biopsies obtained from chronic hepatitis C patients and 84 liver tissues obtained from noncancerous parts of surgically removed HCV-related hepatocellular carcinoma were analysed. Positive cytoplasmic ADI1 in liver biopsies was associated with higher serum HCV-RNA levels (P=0.009). Positive MT1-MMP and ADI1 interaction assessed by co-immunoprecipitation was associated with lower tissue HCV-RNA levels (P=0.009). Hepatic HCV-RNA levels were positively associated with ADI1 levels in the MT1-MMP and ADI1 co-immunoprecipitates (P=0.030). Overexpression of MT1-MMP in Huh7.5 cells suppressed cell entry of HCV pseudoparticles as well as HCVcc infection. The suppression effect could be reversed by co-expression of ADI1 in a dose-dependent manner. In summary, clinical and cell-based experiments suggested that physical interaction between MT1-MMP and ADI1 led to suppression of HCV infection. This inhibitory effect could be reversed by ADI1 overexpression.

The efficacy and prognostic predictors of different treatment courses with pegylated interferon α-2a and ribavirin combination in recurrent chronic hepatitis C patients

To study the efficacy and outcome predictors of combined re-treatment with pegylated interferon (Peg-IFN) α-2a and ribavirin in recurrent chronic hepatitis C (CHC) patients. A multicenter, prospective, randomized trial was designed. A total of 125 recurrent CHC patients were recruited in 16 clinical centers and randomly assigned into two groups: one was Peg-IFNα-2a combined with ribavirin for 48 weeks (group A) and the other the same combination for 72 weeks (group B). HCV RNA levels in patients' serum were detected at baseline, week 4, 12, 24, 48, 72 (group B) after treatment initiation, and 24 weeks after treatment. Of all the 90 patients who completed treatment and 24 weeks follow-up, 80.0% achieved sustained virological response (SVR) yet 12.2% relapsed. There was no significant difference between two groups. The SVR rate in patients previously treated with interferon alone was higher than that in patients with interferon plus ribavirin (92.6% vs 74.6%), but the difference was of no statistical significance (P = 0.05). Moreover, patients previously treated with common interferon (c-IFN) showed a higher SVR rate than patients with Peg-IFN (84.7% vs 71.0%, P > 0.05). The positive predictive value (PV) of rapid virological response (RVR) and complete early virological response for SVR was 92.3% and 86.4% respectively, and the negative PV of RVR, early virological response and delayed virological response for SVR was 36.8%, 66.7% and 100.0% respectively. Overall, 62.1% patients reported adverse events (AEs) and 1.6% patients were severe AEs. A high SVR rate has been achieved in recurrent CHC patients who were retreated with Peg-IFNα-2a and ribavirin for 48 weeks. Better SVR cannot be achieved in spite of a prolonged course of 72 weeks. Early virological response at week 12 was the most important predictor for SVR.