Serum Hepatitis C Virus RNA Levels Research Articles

Antiviral activity of lactoferrin: a focus on hepatitis C chronic

Introduction: The Hepatitis C virus (HCV) is one of the main causes of chronic liver disease in the world, and despite having a treatment with sustained virologic response rate, this therapy is not resolutive for all patients. Objectives: To carry out a literature review on the action of bovine lactoferrin (bLf) on chronic hepatitis C to find evidence of its antiviral effect for a possible treatment associated with conventional therapy. Methodology: 49 articles were found according to the descriptors “lactoferrin” “immunotherapy” “chronic hepatitis C” in the pre-selected databases and seven were chosen according to the inclusion and exclusion criteria for writing the review in question. Results: The benefit of bLF use was related to the reduction of serum HCV RNA levels (1106 kIU/ml to 612 kIU/ml), plasma 8-isoprostane (8.6 ± 3.7 to 6.9 ± 2.1 pg/ml) and alanine aminotransferase (ALT) values (85 ± 80 to 63 ± 55 IU/l). Conclusion: The studies showed a possible antiviral effect of bovine lactoferrin that should be explored, through further studies, for adjuvant use in patients with chronic hepatitis C who do not show complete efficacy with the pre-established treatment for the disease.

Feasibility of immunotherapy in cancer patients with persistent or past hepatitis B or C virus infection.

Background and AimImmune checkpoint inhibitors (ICIs) can cause immune‐related adverse events in the liver. The risk of exacerbating liver injury is of concern in patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), as immunotherapy can damage liver function because of the immune response against viral antigens. We assessed the feasibility of immunotherapy in HBV‐ or HCV‐infected patients.MethodsThis retrospective study included 266 patients with persistent or past HBV infection, 26 patients seropositive for anti‐HCV, and 820 patients with negative viral markers for HBV and HCV, who were treated with ICIs. ICI‐induced liver injury and changes in virological markers were analyzed.ResultsThe occurrence rates of ICI‐induced liver injury in the HBsAg‐positive, anti‐HBc‐positive/anti‐HBs‐positive, and anti‐HBc‐positive/anti‐HBs‐negative groups were 12.5, 21.6, and 19.1%, respectively, which were comparable with those of the negative for HBV‐ and HCV‐related markers group (20.9%). The frequency of any grade ICI‐induced liver injury was different among the HCV RNA‐positive (3/5; 60.0%), anti‐HCV‐positive/HCV RNA‐negative (2/21; 9.5%), and negative for HBV‐ and HCV‐related markers (171/820; 20.9%) groups (P = 0.045), with no significant difference in grade ≥2 ICI‐induced liver injury. In patients with persistent infection, neither serum HBV DNA, HBsAg, nor HCV RNA level changed significantly during ICI treatment. One of five treatment‐naïve HCV‐infected patients required interruption of ICI treatment due to virus‐related liver injury.ConclusionImmunotherapy is feasible for most cancer patients with chronic HBV or HCV infection; however, liver function and virological markers should be carefully monitored in treatment‐naïve patients, especially those with HCV infection, during ICI treatment.

Safety and efficacy of grazoprevir/elbasvir in the treatment of acute hepatitis C in hemodialysis patients.

Treatment of hepatitis C virus (HCV) infection with direct‐acting antiviral agents (DAAs) in hemodialysis patients requires extensive consideration. At present, studies regarding DAAs for acute HCV infection in such patients are limited. The present study aims to evaluate the efficacy and safety of grazoprevir (GZR) plus elbasvir (EBR) treatment in acute hepatitis C (AHC) patients undergoing hemodialysis. Patients undergoing hemodialysis who had a nosocomial acute HCV infection were enrolled. All patients received GZR 100 mg/EBR 50 mg once daily for 12 weeks and were followed up for 12 weeks. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and HCV RNA levels were monitored during treatment and follow‐up periods. Sustained virologic response at 12 weeks after treatment cessation and treatment‐emergent adverse events (AEs) were assessed. A total of 68 AHC patients were enrolled. All patients were infected with HCV genotype 1b and achieved SVR12. Decreasing ALT, AST, and TBIL were observed over time in the first 4 weeks and became steady thereafter. Forty‐eight (70.59%) patients reported at least one AEs. The most common AEs were fatigue, headache, and nausea. Two AHC patients discontinued treatment due to serious but drug‐unrelated AEs. In conclusion, GZR/EBR has a high efficacy and safety profile in hemodialysis‐dependent patients with genotype 1b AHC.

HCV RNA in serum and liver samples of patients undergoing living donor liver transplantation.

ObjectiveTo compare hepatitis C virus (HCV) RNA levels from serum and explanted native liver samples from patients undergoing living donor liver transplantation (LDLT).MethodsThis was a prospective observational study. Serum and liver samples were collected from consecutive serum anti-HCV-positive transplant recipients between February 2016 to August 2019. HCV RNA was extracted from liver samples and subjected to one-step reverse-transcription qPCR. using the TopScript One Step qRT-PCR Probe Kit with HCV qPCR probe assay and human GAPDH qPCR probe assay on a ViiA7 Real-Time PCR System.ResultsAmong the 80 patients, 36% (29/80) were HCV RNA positive in serum and 85% (68/80) had positive hepatic HCV RNA. Post-liver transplantation, 4% (3/80) patients were serum positive.ConclusionsOur study suggests that pre-transplant serum HCV RNA levels may give an underestimate of the number of positive HCV RNA cases and that hepatic HCV RNA data may be more accurate.

Hepatitis C Treatment by Directly Acting Antiviral Agents and Its Impact on Glycemic Control

Objective: To evaluate Hepatitis C treatment by directly acting antiviral agents and its impact on glycemic control. 
 Study Design: This is an observational study.
 Setting: This study was conducted in Medicine department Civil Hospital Karachi from March 2018 to December 2019.
 Materials and Methods: Patients visiting the outpatient department of the hospital having documented HCV infection having type 2 diabetes mellitus were included in the study. All participants were given directly acting antiviral treatment for 12 weeks. After treatment they were assessed for achievement of sustained virological response (SVR). Pre-treatment and post treatment fasting blood glucose levels and HbA1c levels were checked. SVR is defined as serum HCV RNA which is undetectable (<50IU/ml) after 12 weeks of antiviral treatment.
 Results: Around 332 patients matched our inclusion criteria. Amongst these there were 219 males and 113 females. The mean age of patients was 39.44 ± 2.19 years. All the selected participants started therapy on Sofosbuvir-velpatasvir (pangenotypic NS5A-NS5B inhibitor single-pill combination regimen that has potent activity against hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, and 6.) plus ribavirin. After treatment with directly acting antiviral therapy 231 (69.57%) patients achieved sustained virological response. Patients who achieved SVR showed improved glycaemic control than those who didn’t. Patients with cirrhosis showed decreased chances of attainment of SVR. Fasting blood glucose levels and HbA1c were also decreased, decreasing the amount of insulin required for diabetes control. 
 Conclusion: Our study showed that treatment with directly acting antiviral treatment improved glycaemic control in HCV infected patients. Other factors like BMI, presence of cirrhosis, mean serum HCV RNA levels and adherence to treatment were major predictors for achievement of SVR.

Novel drug resistance-associated substitutions against pibrentasvir emerged in genotype 1b hepatitis C virus-infected human hepatocyte transplanted mice

Combination therapy with glecaprevir and pibrentasvir (PIB) has high efficacy for patients with hepatitis C virus (HCV) infection except among those who experienced NS5A-P32 deletion (del) mutation during prior DAA treatment failure. However, some patients fail to achieve SVR through combination treatment even in the absence of NS5A-P32del. We analyzed emergence of NS5A resistance-associated substitutions (RASs) against PIB using HCV-infected mice. Male human hepatocyte transplanted mice were infected with genotype 1b wild-type HCV. Mice were treated with PIB, resulting in a transient decrease in serum HCV RNA levels but followed by relapse during the treatment. Direct sequence analysis showed emergences of various mutations in the NS5A region, including L31V/P32del, L31F/P32del/Y93H, NS5A-P29del/Y85C, and NS5A-F37Y. PIB was less effective in mice with NS5A-F37Y mutations compared to mice with wild-type HCV. NS5A-F37Y showed 5.4-fold resistance to PIB relative to wild-type based on analysis using HCV subgenomic replicon systems. The present in vivo and in vitro studies identified NS5A-F37Y as a novel RAS against PIB and showed the possibility of emergence of various NS5A RASs including P29del, P32del and F37Y following PIB treatment. These mutations might emerge and lead to failure to respond to DAA therapies including PIB-based regimens in chronic hepatitis C patients.

Histopathology and the predominantly progressive, indeterminate and predominately regressive score in hepatitis C virus patients after direct-acting antivirals therapy.

BACKGROUNDHistological changes after direct-acting antivirals (DAAs) therapy in hepatitis C virus (HCV) patients has not been elucidated. Whether the predominantly progressive, indeterminate and predominately regressive (P-I-R) score, evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIMTo identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODSChronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included. Sustained virologic response (SVR) was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation. The Ishak system and P-I-R score were assessed. Inflammation improvement and fibrosis regression were defined as a ≥ 2-points decrease in the histology activity index (HAI) score and a ≥ 1-point decrease in the Ishak fibrosis score, respectively. Fibrosis progression was defined as a ≥ 1-point increase in the Ishak fibrosis score. Histologic improvement was defined as a ≥ 2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy. The P-I-R score was also assessed. “absolutely reversing or advancing” was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score; and “probably reversing or advancing” was defined as only one parameter showing directionality.RESULTSThirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included. The mean age of these patients was 40.9 ± 14.6 years and there were 53% (20/38) males. Thirty-four percent (13/38) of patients were cirrhotic. Eighty-two percent (31/38) of patients achieved inflammation improvement. The median HAI score decreased significantly after SVR (pretreatment 7.0 vs posttreatment 2.0, Z = -5.146, P = 0.000). Thirty-seven percent (14/38) of patients achieved fibrosis improvement. The median Ishak score decreased significantly after SVR (pretreatment 4.0 vs posttreatment 3.0, Z = -2.354, P = 0.019). Eighty-two percent (31/38) of patients showed histological improvement. The P-I-R score was evaluated in 61% (23/38) of patients. The progressive group showed lower platelet (P = 0.024) and higher HAI scores (P = 0.070) before treatment. In patients with stable Ishak stage after treatment: Progressive injury was seen in 22% (4/18) of patients, 33% (6/18) were classified as indeterminate and regressive changes were seen in 44% (8/18) of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSIONSignificant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy. The P-I-R score has potential in predicting fibrosis in HCV patients.

Prevalence and characteristics of hepatitis C virus infection in Shenyang City, Northeast China, and prediction of HCV RNA positivity according to serum anti-HCV level: retrospective review of hospital data

ObjectiveThe prevalence of hepatitis C virus (HCV) infection is typically evaluated based on the current rate of positivity of anti-HCV antibody; however, HCV RNA positivity is considered the main criterion for antiviral treatment of HCV infection in the clinical setting. In this study, we evaluated the prevalence of HCV infection based on anti-HCV and HCV RNA detection in the population of Liaoning Province, and investigated the correlation between serum HCV RNA positivity and anti-HCV levels.MethodsA total of 192,202 patients who underwent serum anti-HCV examination at Shengjing Hospital in 2018 were enrolled in the study. Anti-HCV production was tested using a chemiluminescence assay, and serum HCV RNA detection was performed with Roche COBAS TaqMan (CTM) Analyzer.ResultsThe prevalence of anti-HCV was 1.21 and 0.93% among male and female patients in Liaoning Province, respectively. The positive rates of anti-HCV and serum anti-HCV levels were both age-related, in which patients over 40 years of age had a significantly higher anti-HCV positive rate than those younger than 40 years. Among the anti-HCV-positive patients, the average HCV RNA positive rate was 51.66 and 35.93% in males and females, respectively. Spearman rank analysis showed a significantly positive correlation between serum HCV RNA positivity and the level of anti-HCV. The best cut-off value using serum anti-HCV levels to predict the positivity of HCV RNA was determined to be 9.19 signal-to-cut-off ratio (s/co) in males and 10.18 s/co in females.ConclusionThe prevalence of anti-HCV in the general population of Liaoning Province was around 1.04%, which was higher than that previously reported from a national survey of HCV infection in China. Approximately 42.9% of the anti-HCV-positive patients also tested positive for HCV RNA. However, the positive correlation between the serum anti-HCV and HCV RNA levels suggests that the positivity of serum HCV RNA can be predicted according to the anti-HCV level in anti-HCV-positive patients, which can improve screening and facilitate timely intervention to prevent the spread of infection.

Ledipasvir/Sofosbuvir in Adolescents With Chronic Hepatitis C Genotype 4 With and Without Hematological Disorders: Virological Efficacy and Impact on Liver Stiffness.

Egypt has the highest prevalence of hepatitis C virus (HCV) infection. Anti-HCV antibodies were detectable in 3% of children in Upper Egypt. Our aim was to evaluate the efficacy of ledipasvir/sofosbuvir for chronic HCV genotype 4 in adolescents with/without hematological disorders and to determine the effect of sustained virological response (SVR) on liver stiffness. Sixty-five adolescents were recruited. There were 3 patient groups: group 1, 44 treatment-naive without hematological disorders; group 2, 6 previously treated; and group 3, 15 treatment-naive with hematological disorders. All patients received sofosbuvir 400 mg/ledipasvir 90 mg per day for 12 weeks. Serum HCV RNA levels were measured before treatment, at week 12, and at 12 weeks after the end of treatment (SVR12). Liver stiffness and the aspartate aminotransferase-platelet ratio index (APRI) score were estimated at baseline and at SVR12. SVR12 was 100%. At SVR12, there was a significant improvement in liver stiffness in all groups. The APRI score showed significant improvements in groups 1 and 3 (P < .001 and P = .004, respectively). The treatment was well tolerated, with minimal and self-limited side effects. Treatment of chronic HCV in adolescents using ledipasvir/sofosbuvir was effective, with a cure rate (at SVR12) of 100%. Significant improvement in liver stiffness was found in all groups.

Ribavirin induces hepatitis C virus genome mutations in chronic hepatitis patients who failed to respond to prior daclatasvir plus asunaprevir therapy.

Ribavirin (RBV) induces nucleotide (nt) substitutions in hepatitis C virus (HCV) genome nonstructural (NS) regions. Although emergence of drug resistance-associated variants is associated with direct-acting antiviral treatment failure, the effect of RBV on genome substitutions in such patients is unknown. Genotype 1b HCV subgenomic replicon cells were treated with RBV for 120 hours. Six patients with chronic genotype 1b with HCV-infected patients who failed to respond to prior daclatasvir plus asunaprevir (DCV/ASV) therapy were treated with 12 weeks of sofosbuvir and ledipasvir plus RBV after 4 weeks of RBV monotherapy. RBV-induced genome mutations in the HCV NS region (nt3493-9301) in replicon cells and in patients during 4 weeks of RBV monotherapy were analyzed by deep sequencing. RBV-associated G-to-A and C-to-U transitions increased in a dose-dependent manner in HCV replicon cells after the RBV treatment. In patients with prior DCV/ASV treatment failures, the median serum HCV RNA level was 6.25 ± 0.31 log IU/mL at the start of RBV therapy and decreased significantly to 5.95 ± 0.4 log IU/mL (P = .03) after 4 weeks of RBV monotherapy. Although predominant HCV genome substitutions rates were similar between nontreatment and RBV-treatment periods (0.042 and 0.031 per base pair, respectively; P = .248), the frequencies of G-to-A and C-to-U transitions significantly increased after RBV monotherapy. These transitions were enriched, particularly within the HCV NS3 region in all patients. RBV treatment induces G-to-A and C-to-U transitions in the HCV genome even in chronic patients with hepatitis C with prior DCV/ASV treatment failures.

Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals.

BACKGROUNDCurrent diagnosis of hepatitis C virus (HCV) infection requires two sequential steps: testing for anti-HCV followed by HCV RNA PCR to confirm viremia. We have developed a highly sensitive and specific HCV-antigens enzyme immunoassay (HCV-Ags EIA) for one-step diagnosis of viremic HCV infection.AIMTo assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus (HIV)-coinfected individuals.METHODSThe study blindly tested HCV-Ags EIA for its performance in one-step diagnosing viremic HCV infection in 147 sera: 10 without HCV or HIV infection; 54 with viremic HCV monoinfection; 38 with viremic HCV/HIV coinfection; and 45 with viremic HCV and non-viremic HIV coinfection.RESULTSUpon decoding, it was 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR test. In five sera with HCV infection, HCV RNA was as low as 50-59 IU/mL, and four out of five tested positive for HCV-Ags EIA. Likewise, it was also 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR in 83 sera with HCV and HIV coinfection, regardless if HIV infection was active or not.CONCLUSIONThe modified HCV-Ags EIA has a lower detection limit equivalent to serum HCV RNA levels of approximately 100 IU/mL. It is highly sensitive and specific in the setting of HIV coinfection, regardless of HIV infection status and CD4 count. These data support the clinical application of the HCV-Ags EIA in one-step diagnosis of HCV infection in HIV-infected individuals.

Identification of IL-10-secreting CD8+CD28−PD-1+ regulatory T cells associated with chronic hepatitis C virus infection

CD8+CD28− regulatory T cells (Tregs) play important roles in chronic viral infections. Programmed death 1 (PD-1) is highly expressed on hepatitis C virus (HCV)-specific CTLs. However, little is known regarding the role of CD8+CD28-PD1+ T cells in hepatitis C. Herein, we found that the frequency of CD8+CD28−PD1+, but not CD8+CD28−PD1− T cells, correlated with markers of chronic hepatitis C virus (HCV) infection and the response to treatment. Our results showed that CD8+CD28-PD1+ T cells were significantly elevated in chronic HCV-infected patients and there was a distinct correlation between the frequency of CD8+CD28-PD1+ T cells and serum levels of HCV RNA. During a 48-week course of treatment with peg-IFN-a2a plus ribavirin, dynamic changes in the frequencies of CD8+CD28-PD1+ T cells were observed, associated with the virologic response. IL-10 secretion may explain the suppressive function of CD8+CD28-PD1+ T cells in chronic HCV-infected patients. Overall, our study demonstrates that PD-1 is an important marker of CD8+CD28− Tregs in chronic HCV infection. Thus, the frequency and regulatory function of CD8+CD28-PD1+ T cells play vital roles in HCV infection and the response to treatment.

Effectiveness and safety of simeprevir-based regimens for hepatitis C in Italy: The STIly observational study.

The combination of the direct-acting antivirals, simeprevir (SMV) and sofosbuvir (SOF), was the first highly efficacious interferon-free combination for treating patients with hepatitis C virus (HCV), and was widely used in Italy as a result.The aim of this study was to evaluate effectiveness and safety of SMV in Italian patients with HCV genotype (GT) 1 and 4 overall, by treatment regimen [SMV/SOF and SMV/SOF+ribavirin (RBV)], cirrhosis status, and GT (GT1a, GT1b, and GT4).An observational multicenter cohort study was conducted in 46 centers across Italy. Adult HCV + GT1 or GT4 patients, naive or treatment-experienced, with or without cirrhosis, who underwent treatment with a SMV-containing regimen from May to September 2015 were included. The primary endpoint was sustained virologic response (SVR), defined as undetectable serum HCV RNA levels 12 weeks after treatment end (SVR12). The secondary endpoints included duration of treatment, safety and tolerability of each treatment regimen, and SVR by treatment and according to response to previous treatment and fibrosis stage. The association between SVR and a subset of the most clinically relevant variables was investigated by a multivariate logistic regression analysis.A total of 349 HCV-positive patients treated with an SMV-based regimen were enrolled, of whom 342 received SMV/SOF ± RBV and were included in this analysis. Most patients (59.4%) were treatment-experienced and had cirrhosis (78.1%). In the group receiving SMV/SOF + RBV, most (63.1%) were treatment-experienced and 82.9% had cirrhosis. Three patients were lost to follow-up; 330 patients receiving SMV/SOF ± RBV (96.5%) were treated for 12 weeks. Overall, SVR12 was achieved by 324 patients [94.2%, 95% confidence interval (95% CI) 92-97]. When stratified by treatment and clinical and virologic characteristics, SVR12 was achieved by 77 of 79 [97.5% (95% CI 94.0-100.0)] and 247 of 263 [93.9% (95% CI 91.0-96.8)] patients receiving SMV/SOF and SMV/SOF + RBV, respectively; 132 of 139 (95.0%) naive versus 192/203 (94.6%) treatment-experienced patients; 250 of 267 (93.6%) cirrhotic and 56 of 62 (90.3%) HIV coinfected patients. SMV-based regimens were generally well tolerated. Adverse events leading to treatment discontinuations were not observed.A high proportion of patients treated with SMV/SOF-based regimens achieved SVR12 in this study. A high SVR12 rate was also achieved in patients with cirrhosis, treatment experience, and HUV coinfected patients.

A natural small molecule inhibitor corilagin blocks HCV replication and modulates oxidative stress to reduce liver damage

Hepatitis C virus (HCV) infection causes chronic liver disease, which often leads to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against viral hepatitis. Here, we report identification of a principal bioactive component ‘corilagin’, which showed significant inhibition of the HCV key enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound could effectively inhibit viral replication in the infectious cell culture system, displayed strong antioxidant activity by blocking HCV induced generation of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-β mRNA levels. Oral administration of corilagin in BALB/c mice demonstrated its better tolerability and systemic bioavailability. More importantly, corilagin could restrict serum HCV RNA levels, decrease collagen deposition and hepatic cell denaturation in HCV infected chimeric mice harbouring human hepatocytes. Taken together, results provide a basis towards developing a pure natural drug as an alternate therapeutic strategy for restricting viral replication and prevent liver damage towards better management of HCV induced pathogenesis.

Hepatitis C viral load, genotype, and increased risk of developing end-stage renal disease: REVEAL-HCV study.

This study reveals that chronic HCV infection is associated with an increased risk of developing ESRD and suggests that elevated serum levels of HCV RNA (>167,000 IU/mL) and HCV genotype 1 are strong predictors of ESRD, indicating clinical implications for the management of chronic HCV. (Hepatology 2017;66:784-793).

Biopsy Specimens From Allograft Liver Contain Histologic Features of Hepatitis C Virus Infection After Virus Eradication.

Most patients, even those who have received a liver transplant, achieve a sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection. Little is known about the histologic features of liver biopsy specimens collected after SVR, particularly in patients who have received a liver transplant. We aimed to better characterize the histologic features of allograft liver biopsy specimens from patients who achieved SVR to anti-HCV therapy after liver transplantation. We performed a retrospective analysis of 170 allograft liver biopsy specimens from 36 patients who received a liver transplant for chronic HCV infection, had recurrent HCV infection after transplantation, and subsequently achieved SVR (collected from 1999 through 2015 at 4 medical centers). SVR was defined as an undetectable serum HCV RNA level 24 weeks after completion of HCV treatment. A total of 65 biopsy specimens were post-SVR (at least 1 post-SVR from each patient; some biopsy specimens were collected at later time points from a subset of patients). We performed polymerase chain reaction analysis for HCV RNA on a subset of the biopsy specimens (28 collected before SVR and 32 after SVR). Of the 65 post-SVR biopsy specimens, 45 (69%) had histologic features of active HCV infection. Of the initial post-SVR biopsy specimens collected from each of the 36 patients, 32 (89%) showed these changes. For patients with more than 1 post-SVR biopsy specimen, 6 (46%) had no change in fibrosis between biopsies, and fibrosis worsened for 3 patients (23%) based on their most recent biopsy. The HCV RNA level was undetectable in 31 of the 32 biopsy specimens analyzed by polymerase chain reaction. In a retrospective analysis of allograft liver biopsy specimens from patients who achieved SVR after a liver transplant for chronic HCV infection, histologic changes associated with active HCV were present in 69% and fibrosis continued to progress in 23%, despite the lack of detection of HCV RNA. Pathologists should be aware of patients' SVR status when analyzing liver biopsy specimens to avoid diagnoses of chronic HCV-associated hepatitis. Because of the persistent inflammatory activity and fibrosis after SVR, clinicians should continue to monitor patients carefully after SVR to anti-HCV therapy.

Assessment of Hepatitis C Virus RNA in Peripheral Blood Mononuclear Cells as a Predictor of Response to Pegylated-Interferon and Ribavirin: A Cohort Study

Background: Sustained virologic response (SVR) to pegylated-interferon (PegIFN) and ribavirin (RBV) in hepatitis C virus (HCV)-infected patients could be predicted by detection of serum HCV RNA whereas detection of HCV RNA in other reservoirs such as peripheral blood mononuclear cells (PBMCs) for prediction of treatment response is still a mystery. Objectives: This study aimed at assessing the prediction of SVR by detection of HCV RNA in PBMCs or serum in patients during treatment. Methods: In a cohort study (2011 to 2014), 100 chronic HCV patients at Tehran Hepatitis Center were treated with PegIFN and RBV. Serum HCV RNA level was measured at baseline, 4, 12, and 24 weeks during treatment and at 24 weeks after termination of treatment. Meanwhile, HCV RNA was evaluated in PBMCs at weeks 4, 12, and 24 during the treatment. Results: Out of 100 patients treated in this study, 91 completed the course of treatment. Most patients were young males infected with HCV genotype 1. Cirrhosis and previous history of treatment was found in 16.5% and 26.5% of patients. Sustained virologic response was achieved in 65 (71.4%) patients. Among baseline parameters, only female gender was significantly associated with SVR. Undetectable serum HCV RNA at week 4 (OR = 4.74) and week 12 (OR = 11.63) of treatment predicted SVR rate while the same was not true for detection of serum HCV RNA at week 24 of treatment. Moreover, detection of HCV RNA in PBMCs at weeks 4 and 12 of treatment was not associated with the rate of SVR, while absence of HCV RNA in PBMCs at week 24 of treatment was associated with SVR (OR = 4.55). Conclusions: Detection of HCV RNA in PBMCs, especially at week 24 of treatment with PegIFN and RBV, could be considered as an additional marker for prediction of treatment response. It is recommended to assess HCV on-treatment kinetic in PBMCs of patients treated with direct-acting antiviral agents for prediction of treatment response.

Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C.

BackgroundThe current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients.MethodsThirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR.ResultsOur study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed.ConclusionLncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C.

Hepatitis C virus load in parenchyma cells correlates with hepatic injury in infected patients

The association between serum hepatitis C virus (HCV) load and hepatic injury in HCV-infected patients has been extensively investigated. The present study aimed to investigate the association between HCV load in hepatic parenchyma cells and hepatic injury in HCV-infected patients. A total of 56 HCV-infected patients were included in the present retrospective study. The serum HCV mRNA was determined using quantitative polymerase chain reaction, while the hepatic parenchyma cell volume and HCV mRNA in hepatic parenchyma cells were also determined. Hepatic injury was evaluated on the basis of the severity of inflammation and fibrosis. The results demonstrated that there were evident differences in the mean serum HCV RNA levels and the HCV load/parenchyma cell volume among the various grades of hepatic inflammation (G1-G4) when groups with the least and most inflammation were compared (G1 vs. G4; P<0.05). Significant differences in the HCV load existed between groups divided according to the fibrosis grade; in addition, differences existed between fibrosis grades S1 and S2, and S2 and S4 when comparing serum HCV RNA levels (P<0.05). Similarly, differences existed between every two fibrosis stages (S0 vs. S4, S2 vs. S3, and S2 vs. S4; P<0.05) when viral loads and parenchyma cell volumes were compared (F=2.860, P<0.05). Furthermore, the fibrosis staging was correlated with the viral load/parenchyma cell volume (F=2.670, P<0.05). In conclusion, hepatic fibrosis grade was found to be associated with HCV load in parenchyma cells. The results of the present study demonstrated that the viral load in parenchyma cells is a more appropriate index compared with the serum viral load for evaluating HCV replication in hepatocytes, and may function as an important factor in HCV-infected hepatic injury evaluation.

Serum CXCL-10 level in chronic hepatitis C patients with cryoglobulinemia and its influence on antiviral therapy

Objective: To investigate the serum CXCL-10 level in chronic hepatitis C (CHC) patients with cryoglobulinemia and its influence on the effect of antiviral therapy. Methods: A total of 50 CHC patients were enrolled in the study. Cryoprecipitation was used to determine the nature of cryoglobulins in serum before treatment, and ELISA was used to measure the serum CXCL-10 level. The hepatitis C virus (HCV) genotype was detected, and serum HCV RNA level was measured at baseline, 4, 12, and 24 weeks of treatment, the end of treatment, and 24 weeks after treatment.. Results: Compared with the cryoglobulin-negative patients, the cryoglobulin-positive patients had significantly higher baseline levels of HCV RNA [(6.28±0.79) log10 copies/ml vs (5.48±1.20) log10 copies/ml, P = 0.009] and CXCL-10 (541.67±224.07 pg/ml vs 394.39±179.71 pg/ml, P = 0.015). After the treatment with pegylated interferon-α-2a and ribavirin, the cryoglobulin-positive patients had a significantly lower proportion of individuals who achieved rapid virological response compared with the cryoglobulin-negative patients (33.3% vs 82.6%, P < 0.001). The cryoglobulin-positive patients had a significantly lower rate of sustained virologic response than the cryoglobulin-negative patients (33.3% vs 78.3%, P = 0.001). Conclusion: The patients with cryoglobulinemia have higher serum levels of HCV RNA and CXCL-10 and poor outcomes compared with those without cryoglobulinemia.