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Scientific relevance. The absence of blood-borne viruses in human plasma-derived medicinal products must be ensured by the control of raw materials and the manufacturing process.Aim. This study aimed to analyse system suitability criteria for analytical procedures to assess the viral safety of individual units of the substance "Human plasma for fractionation" in terms of the content of nucleic acids of blood-borne viruses, considering the requirements of the European Pharmacopoeia.Materials and methods. The authors analysed individual units of the substance "Human plasma for fractionation" (hereinafter, plasma). The study used the International Standards (ISs) for human immunodeficiency virus RNA, hepatitis A virus (HAV) RNA, hepatitis C virus (HCV) RNA, hepatitis B virus (HBV) DNA, and parvovirus B19 DNA, as well as nucleic acid detection kits for these viruses based on polymerase chain reaction (PCR).Results. HCV RNA was not detected in any of the eight plasma samples studied, and parvovirus B19 DNA was detected in one of the samples at a concentration not exceeding 104 IU/mL. Three tests with the corresponding ISs showed that the studied reagent kits detected HCV RNA at a concentration of 102 IU/mL and parvovirus B19 DNA (M1 genotype) at a concentration of 104 IU/mL. In additional tests that were conducted in two samples considering the requirements of the European Pharmacopoeia for the detection of HCV RNA and parvovirus B19 DNA, a new batch of reagent kit I detected the HCV RNA IS at a concentration of 102 IU/mL only in one of three replicates, which did not correspond to the claimed sensitivity of the reagent kit. HCV RNA was not detected in either replicate in one of two plasma samples spiked with the HCV RNA IS at concentrations of 102 and 103 IU/mL, possibly because of plasma inhibitory properties. The sensitivity of the reagent kits to parvovirus B19 DNA corresponded to the label claims; the study did not show any inhibitory properties of the plasma samples.Conclusions. Polymerase chain reaction testing of the viral safety of plasma intended for manufacturing medicinal products should include control samples calibrated in IU/mL. Further research and appropriate pharmacopoeial reference materials are needed to set system suitability criteria for analytical procedures using such control samples.

With the increase in the number of patients with sustained virologic response (SVR) in whom hepatitis C virus (HCV) was eradicated by the anti-HCV therapy, there are now many individuals in whom serum HCV RNA is absent despite positive serum HCV antibodies. However, in general clinical practice, HCV infection remains usually screened by measurement of serum HCV antibodies and patients with SVR can be misunderstood regarding HCV infection status. In the multicenter study, we conducted interviews with administered questionnaires to SVR individuals who had regular hospital visits after SVR. The prevalence of experiencing an incorrect diagnosis of HCV infection after SVR was assessed. Individuals who experienced this misunderstanding were further asked where they experienced it and how it made them feel. In a survey of 2,246 SVR individuals, 197 individuals (8.8%) were misunderstood as having persistent HCV infection by medical doctors due to positive HCV antibody, despite the absence of HCV viremia. These misunderstandings occurred most prevalently at a private clinic (55.3%). More than half (53.3%) of these individuals felt anxious about their HCV infection with becoming unsure about their HCV eradication status. Misunderstanding HCV status is commonly occurred in SVR individuals. Specialists in hepatology and infectious diseases should broadly emphasize the fact that most patients with HCV antibodies are now HCV-free because of the use of anti-HCV therapy. [ABSTRACT FROM AUTHOR]

Background and aim: To observe the clinical value of hepatitis C virus (HCV) core antigen (HCcAg) levels in monitoring acute HCV infection in patients with spontaneous clearance (SC) or clearance induced by antiviral therapy. Methods: Patients with iatrogenic HCV infection (n = 104) were enrolled at the Shengjing Hospital, China Medical University, between 5 February 2013 and 3 April 2013. All cases were diagnosed with acute HCV infection, enrolled within 90 days of infection, and followed for 12 to 16 weeks. Blood was collected every month. HCV RNA and HCcAg levels were detected. From week 16, patients without SC were treated with pegylated‐interferon and the HCV RNA and HCcAg levels were observed monthly. Follow‐up was 7.5 (5.0 to 10.4) months. The Spearman correlation analysis was performed to determine the correlation between HCV RNA and HCcAg. Logistic regression analysis was used to determine the association of baseline HCV RNA and HCcAg levels with SC. Results: Ten patients (9.62%) showed SC, with a negative conversion time of 57 (14 to 143) days. During follow‐up, HCV RNA and HCcAg expression levels were positively correlated for each patient (except on the sixth month), but the levels of HCV RNA and HCcAg were not associated with HCV infection SC. Conclusions: HCcAg levels could be of value for monitoring the course early HCV infection, but could not predict SC of HCV infection. [ABSTRACT FROM AUTHOR]

A digital detection strategy based on a portable personal glucometer (PGM) was developed for the simple, rapid, and sensitive detection of hepatitis C virus (HCV) RNA, involving the release of glucose-loaded nanoliposomes due to coupling-site-specific cleavage by the endonuclease BamHI. The glucose-loaded nanoliposomes were synthesized using a reversed-phase evaporation method and provided an amplified signal at the PGM in the presence of HCV RNA. Initially, a 21-mer oligonucleotide complementary to HCV RNA was covalently conjugated to a magnetic bead through the amino group at the 5′ end of the oligonucleotide, and then bound to a glucose-loaded liposome by typical carbodiimide coupling at its 3′ end. In the presence of the target HCV RNA, the target hybridized with the oligonucleotide to form double-stranded DNA. The symmetrical duplex sequence 5′-GGATCC-3′ between guanines was then catalytically cleaved by BamHI, which detached the glucose-loaded liposome from the magnetic bead. Following magnetic separation of the bead, the detached glucose-loaded liposome was lysed using Triton X-100 to release the glucose molecules within it, which were then detected as an amplified signal at the digital PGM. Under optimal conditions, the PGM signal increased with increasing HCV RNA, and displayed a strongly linear dependence on the level of HCV RNA for concentrations ranging from 10 pM to 1.0 μM. The detection limit (LOD) of the system was 1.9 pM. Good reproducibility and favorable specificity were achieved in the analysis of the target HCV RNA. Human serum samples containing HCV RNA were analyzed using this strategy, and the developed sensing platform was observed to yield satisfactory results based on a comparison with the corresponding results from a Cobas® Amplicor HCV Test Analyzer.A digital detection strategy utilizing a personal glucometer was developed for the detection of hepatitis C virus RNA. The strategy involved the use of the endonuclease BamHI along with a 21-mer oligonucleotide conjugated to both a magnetic bead and a glucose-loaded nanoliposome. Hybridization of the nucleotide with the target RNA triggered the coupling-site-specific cleavage of the duplex by BamHI, leading to the release of the glucose-loaded nanoliposome. Following separation of the magnetic bead, the free nanoliposome was dissolved, liberating the glucose molecules within it, which in turn were detected as an amplified signal by the glucometer [ABSTRACT FROM AUTHOR]

Background/AimsBiochemical parameters and acute-phase proteins (APPs) may provide complementary data in patients with chronic hepatitis C (CHC). We aimed to evaluate the predictive role of APPs in the response to antiviral therapy.Methods : Forty-five patients underwent antiviral therapy. Serum ferritin, C-reactive protein (CRP), transferrin, albumin, alpha-1 acid glycoprotein (A1AG), and alpha-2 macroglobulin (A2MG) levels were examined at the initial evaluation and at the 4th, 12th, and 48th weeks. HCV RNA levels were examined at the initial evaluation and at the 12th and 48th weeks.Results : Ferritin, transferrin, A1AG, and A2MG levels were significantly higher in the patient group (p

The objective of this research was to investigate the clinical performance of COBAS AMPLICOR hepatitis C virus (HCV) test version 2.0 Assays (CA V2.0). Eight serial samples with standard HCV ribonucleic acid (RNA) concentration and 10 times serial dilution of the 500 IU/mL samples were tested in triplicate by CA V2.0 (the limit of detection was 50 IU/mL). HCV RNA was investigated with CA V2.0 in 220 specimens from 100 chronic hepatitis C (CHC) patients, 60 chronic hepatitis B patients, and 60 healthy blood donors. The sensitivity was 99% and the specificity was 98.3%. Sera of 84 naïve CHC patients receiving standard interferon plus ribavirin for 24 weeks were tested by CA V2.0 and CA V1.0 at weeks 2, 4 and 8. The positive detection rates of CA V2.0 were significantly higher than CA V1.0 at week 2 (60.7% vs. 51.2%; p < 0.01) and week 8 (27.4% vs. 21.4%; p < 0.05). At weeks 2, 4 and 8, the positive predictive values were 90.91%, 83.02% and 78.69% with CA V2.0, and 90.24%, 82.14% and 72.73% with CA V1.0. The negative predictive values were 58.82%, 77.42% and 86.96% with CA V2.0, and 67.44%, 82.14% and 83.33% with CA V1.0. However, there was no significant difference between CA V2.0 and CA V1.0 for predicting sustained virologic response.

Fourteen hepatitis C virus (HCV) chronically infected patients were submitted to routine liver biopsy for histological evaluation. Liver samples were assayed to HCV-RNA by in situ hybridization, using digoxigenin labeled probe. HCV genotypes were found to be predominantly type 1 (71.4%), followed by genotype 3 (21.4%), and genotype 2 (7.2%). Alanine-aminotransferase levels were raised in 10 patients. The histopathological scores were minimal (21.4%), mild (57.2%), and moderate (21.4%). Viral RNA was detected in liver cells from nine patients (64.3%). ISH method provides localization and poor confirmation of HCV RNA in the liver tissue of HCV chronic patients.

Background The COBAS ® AmpliPrep ® /COBAS ® TaqMan ® HCV Test, v2.0 (CAP/CTM2) is used for HCV RNA viral load monitoring. Objectives The performance of the CAP/CTM2 was compared to other widely used tests, including a manual version of the assay (the COBAS ® TaqMan ® HCV Test, v2.0 for use with the High Pure System, HPS/CTM2) predominantly used during phase III clinical trials for the new direct acting antiviral therapies. Study design Low HCV RNA level comparisons were performed across tests (Abbott Realtime HCV Test, ART; COBAS ® AmpliPrep ® /COBAS ® TaqMan ® HCV Test, v1.0, CAP/CTM1; CAP/CTM2; and HPS/CTM2) using dilutions of the 2nd HCV WHO International Standard. Additionally, the clinical performance of the CAP/CTM2 was evaluated with 421 leftover HCV RNA-positive routine clinical samples. Results All quantifiable WHO dilutions were within ±0.3 log 10 IU/mL of the expected results across tests and the analytical sensitivity resulted in a limit of detection of 12 IU/mL (95% confidence interval, 10, 15). When clinical samples were tested the results for 87% (367 of 421) of all sample comparisons were within ±0.5 log 10 IU/mL. When low viral load results (25–3500 IU/mL) were compared, values obtained by the ART assay were significantly lower ( p < 0.0001) than those obtained with the CAP/CTM2. Conclusions The new CAP/CTM2 showed good accuracy with comparable sensitivity to comparator assays. The new kit is well-suited for use in the routine diagnostic laboratory, especially for accurate monitoring of patients receiving triple therapy or interferone-free regimens. [ABSTRACT FROM AUTHOR]

Objectives Infection with hepatitis C virus ( HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/ HIV-coinfected individuals. Methods Mixed models were used to analyse the natural history of HCV RNA changes over time in HIV-positive patients with chronic HCV infection. Results A total of 1541 individuals, predominantly White (91%), male (73%), from southern (35%) and western central Europe (23%) and with HCV genotype 1 (58%), were included in the analysis. The median follow-up time was 5.0 years [interquartile range ( IQR) 2.8 to 8.3 years]. Among patients not on combination antiretroviral therapy ( cART), HCV RNA levels increased by a mean 27.6% per year [95% confidence interval ( CI) 6.1−53.5%; P = 0.0098]. Among patients receiving cART, HCV RNA levels were stable, increasing by a mean 2.6% per year (95% CI −1.1 to 6.5%; P = 0.17). Baseline HCV RNA levels were 25.5% higher (95% CI 8.8 to 39.1%; P = 0.0044) in individuals with HCV genotype 1 compared with HCV genotypes 2, 3 and 4. A 1 log HIV-1 RNA copies/mL increase in HIV RNA was associated with a 10.9% increase (95% CI 2.3 to 20.2%; P = 0.012) in HCV RNA. Conclusions While HCV RNA levels increased significantly in patients prior to receiving cART, among those treated with cART HCV RNA levels remained stable over time. [ABSTRACT FROM AUTHOR]

For refractory chronic hepatitis C, interferon (IFN)-based triple-agent combination therapy with second-generation direct-acting antivirals (DAAs) has been established as the standard treatment method. The rate of decrease in the viral load and the negative conversion of hepatitis C virus (HCV) RNA in the early phase following treatment initiation are considered important factors for predicting the therapeutic outcome. In the present study, the Roche Cobas AmpliPrep/COBAS TaqMan (CAP/CTM) HCV v2.0 assay and the AccuGENE m-HCV RNA quantitative assay [Abbott RealTime HCV (ART) assay] were analyzed for their clinical efficacy and ability to predict therapeutic outcomes in the early phase in patients with relapse following IFN-based second-generation DAA therapy. Of the 56 patients who received IFN-based second-generation DAA therapy since December 2013, 6 achieved an end-of-treatment response (ETR), but subsequently experienced relapse. In these 6 patients, fluctuations in viral loads in the early phase detected by the CAP/CTM and ART assays were compared. At 4 weeks after treatment initiation, 4 of the 6 patients were diagnosed as negative by the CAP/CTM assay, whereas 2 of these 4 patients were not identified as negative by the ART assay. Of the 2 patients, one was signal-positive with an HCV RNA load <1.08 Log IU/ml, and the other patient had a viral load of 1.12 Log IU/ml. At 8 weeks after treatment initiation, 1 patient was found to be negative by the CAP/CTM assay, but signal-positive with a viral load <1.08 Log IU/ml by the ART assay. From 4 to 8 weeks after treatment initiation, 3 of the 6 patients appeared to be discrepant cases. In conclusion, of the 6 patients who achieved an ETR, 4 were determined to have achieved a rapid virological response (RVR) by the CAP/CTM assay, but may not have actually become negative. The ART assay is highly sensitive, has a wide measurement range, may be suitable for monitoring HCV RNA loads, and is expected to have an important role in providing a predictive marker for early therapeutic outcomes. In discrepant cases in which no RVR is proved by either assay, it was assumed important to consider continuation of treatment and to attempt to achieve a sustained virological response. [ABSTRACT FROM AUTHOR]

Abstract: Even with the most advanced 3rd-generation assays, the serologic window period of hepatitis C virus (HCV) is approximately 74 days. HCV RNA detection would reduce the risk of transmission during this period. Furthermore, quantitation of HCV RNA is necessary for proper planning of treatment, monitoring disease progression, and assessing response to antiviral therapy. We have standardized an in-house HCV real-time reverse transcriptase polymerase chain reaction (RT-PCR) for screening and accurate quantitation and detection of HCV RNA in plasma samples. The in-house real-time assay was compared with a commercial assay using 100 chronically infected individuals and 70 blood donors who are negative for hepatitis B surface antigen, HCV antibody, and HIV antibody. The lower limit of detection of this in-house HCV real-time RT-PCR as assessed against the World Health Organization (WHO) standard was 50 IU/mL. Interassay and intraassay coefficient of variation ranged from 1.3% to 6.4% and 0.0% to 2.3% respectively. Virus loads as estimated with this in-house HCV real-time assay correlated with the commercial artus HCV RG RT-PCR assay (r = 0.59, P < 0.0001). This assay could be used in screening and monitoring individuals on therapy, showing no genotype-dependent differences in detection. [Copyright &y& Elsevier]

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV-infection complications is based on antiviral therapy with the combination of pegylated interferon-α and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection. These tests diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti-HCV antibody testing and HCV-RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, duration of treatment, dose of ribavirin and virological monitoring procedure. HCV-RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly, the sustained virological response, for example the end point of therapy. [ABSTRACT FROM AUTHOR]

To optimize treatment of chronic hepatitis C early identification of patients who will not achieve a sustained virological response (SVR) is desirable. We investigated hepatitis C virus (HCV) RNA kinetics at day 1 (in 15 patients; genotypes 1 and non-1, 9 and 6 respectively) at weeks 1, 4 and 12 (in 53 patients; genotypes 1 and non-1, 19 and 34, respectively) during treatment with pegylated interferon α-2a and ribavirin. Patients with SVR had a significantly more pronounced mean log10 decline from baseline in HCV RNA levels at weeks 1 and 4 compared with patients who failed to achieve SVR (1.99 vs 0.85 at week 1, P = 0.0003 and 2.89 vs 1.72 at week 4, P = 0.0159), whereas no difference was noted after day 1. For patients with a 2-log10 decrease in HCV RNA levels at day 7, the positive predictive value (PPV) for a SVR was 92%, whereas week 12 was the best time point for predicting a later nonresponse [negative predictive value (NPV) 92%] in patients failing to achieve a 2-log10 drop. For patients with genotype non-1 and a 2-log10 decrease in HCV RNA levels the PPV for a SVR was 89% week 1, and 79% weeks 4 and 12. The corresponding NPV for patients with genotype non-1 were 43, 40 and 100% respectively. During treatment with pegylated interferon α-2a plus ribavirin the HCV RNA decline at week 1 was an accurate predictor of SVR in patients who had achieved a 2-log10 drop in HCV RNA levels, whereas the lack of such decline week 12 was an accurate marker of a nonresponse. [ABSTRACT FROM AUTHOR]

Early virological response may predict outcome following treatment with peginterferon alpha-2a and ribavirin in patients chronically infected with hepatitis C virus (HCV). As total HCV core antigen may constitute an alternative direct marker to HCV RNA for assessing the levels of viraemia in such patients, we evaluated the correlation between HCV core antigen and HCV RNA, and whether HCV core antigen at baseline, 4 and 12 weeks after treatment could predict sustained virological response (SVR) to combined therapy, in comparison with HCV RNA. A total of 290 serum samples from 58 previously treatment naïve chronic HCV patients were examined for HCV core antigen and HCV-RNA by means of quantitative HCV RNA when receiving combination therapy for the first time. SVR was significantly associated with basal HCV core antigen but not with HCV RNA. There was a good correlation between HCV core antigen and HCV RNA ( r2 = 0.781). The negative predictive value of HCV core antigen testing in predicting nonresponse at weeks 4 and 12 were 75 and 100%, and for undetectable or a 2-log drop in HCV RNA were 69.6 and 75% respectively. HCV core antigen detection is quick, and easy to perform alternative to HCV RNA, and could be used as a marker of HCV viraemia for monitoring the progress of therapy. [ABSTRACT FROM AUTHOR]

Recently, a new method of extracorporeal granulocyte depletion apheresis has been developed to treat inflammatory systemic diseases using an Adacolumn (Japan Immunoresearch Laboratories, Takasaki, Japan) that is filled with acetate cellulose beads (G-1 beads) to adsorb the granulocytes. We examined whether hepatitis C virus (HCV) is adsorbed after incubation of the Adacolumn with the sera from patients with HCV-RNA-positive chronic hepatitis C. Patients and Methods: A total of 10 patients with chronic hepatitis C, whose levels of HCV RNA were greater than 800 kIU/ml were examined. The serum was incubated with 500 G-1 beads in a syringe at 37°C for 1 h. After removal of the serum, the beads were washed with RNase-free water. The G-1 beads were removed from the syringe after centrifugation. RNA was extracted from 200 μl of the wash waste and from 10, 50, 100 and 200 beads, respectively, using TRIZol regent. Detection of HCV RNA was performed using the nested PCR method. Results: HCV RNA was detected from as few as 10 G-1 beads. HCV RNA was not detected from waste fluid collected after the last wash from any of the patients. Further, HCV RNA was detected in the initial waste fluid after the 37°C incubation with serum in all of the patients. Since HCV RNA was detected on the G-1 beads, but not from the last washing solution in the current examination, these results suggest that the G-1 beads adsorbed HCV RNA. Conclusions: Our in vitro study confirmed that G-1 beads adsorbed HCV; therefore, apheresis using a column filled with G-1 beads may reduce the HCV RNA load in the blood of patients with chronic hepatitis C. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is an important factor in the development of chronic liver disease and hepatocellular carcinoma. In recent years it has become known that HCV induces various extrahepatic manifestations including mixed cryoglobulinemia, membranoproliferative glomerulonephritis, Sjögren's syndrome, autoimmune thyroiditis, malignant lymphoma, porphyria cutanea tarda and lichen planus. Although the mechanisms of extrahepatic manifestations remain unclear, it is known that interferon (IFN) therapy and coadministration of IFN with ribavirin are effective in promoting the disappearance or alleviation of such extrahepatic lesions, which have tended to be overlooked. The present review focuses on lichen planus, one of the major extrahepatic manifestations.© 2004 Blackwell Publishing Asia Pty Ltd [ABSTRACT FROM AUTHOR]

: Background/AimsUpregulation of interleukin-8 by the hepatitis C virus non-structural-5A-protein leads to inhibition of the antiviral activity of interferon-α in vitro. The clinical significance of interleukin-8 levels for virologic response to interferon-α-based treatment in patients with chronic hepatitis C is unknown.: MethodsWe investigated serum interleukin-8 in 59 healthy controls and 214 patients with chronic hepatitis C (genotype 1, n=152; genotype 2, 3, n=62) and different outcome to interferon-α-based therapy.: ResultsIn patients with chronic hepatitis C higher interleukin-8 levels were observed compared with healthy controls (P<0.0001). Hepatitis C genotype 1-infected patients with early and overall virologic response to interferon-α-based therapy showed lower interleukin-8 levels than non-responders (P=0.025 and P=0.035, respectively). In all patients, elevated interleukin-8 levels were associated with cirrhosis (genotype 1, P=0.0003; genotype 2, 3, P=0.009). Interleukin-8 levels in sustained virologic responders were still higher 24 weeks after the end-of-therapy compared with healthy controls (P<0.0001).: ConclusionsIn genotype 1 infected patients, low pretreatment serum interleukin-8 is associated with virologic response to interferon-α-based therapy. Thus, the conclusion from in vitro studies that the upregulation of interleukin-8 by the hepatitis C virus contributes to the inhibition of the antiviral actions of interferon-α may also be applicable in vivo. [Copyright &y& Elsevier]

: Background/AimsChronic hepatitis C patients infected by genotype 1 are the least responsive to combination therapy and therefore monitoring response is important in identifying non-responders quickly, permitting therapy discontinuation and avoiding side effects and costs. We examined the usefulness of measuring total HCV Core Ag in early treatment with peginterferon α-2b and ribavirin in genotype 1 patients in the prediction of response and compared the results with those from HCV RNA quantification.: MethodsTwo hundred and sixty-eight serum samples from 46 genotype 1 patients receiving combination therapy were examined for HCV Core Ag and quantitative HCV RNA.: ResultsAt baseline, mean HCV RNA and HCV Core Ag concentrations were significantly lower in sustained virologic responders than in non-responders. The negative predictive value of HCV Core Ag testing in predicting non-response at week 12 is 100%, and for a 2 log drop in HCV RNA, using two quantitative tests, it is 88%.: ConclusionsHCV Core Ag determination allows the identification of non-responders with only one test at week 12 and permits stopping therapy in these patients. HCV Core Antigen testing is cheaper and easier to perform than HCV RNA quantification. [Copyright &y& Elsevier]

Background/Aims: To evaluate the efficacy of ribavirin, given in second intention in non-responders to interferon alone, by studying viral kinetics.Methods: We conducted a trial including 203 patients with chronic hepatitis C, naı¨ve of treatment. Patients were treated with interferon three times a week with or without ribavirin and amantadine according to response. Viral kinetics were assessed by serial measurements of HCV RNA (bDNA 3.0 and Monitor 2.0) and a new assay, trak-C, able to quantify total Hepatitis C virus (HCV) core antigen.Results: A significant initial drop in HCV RNA or HCV core antigen, under interferon alone, was associated with response to therapy, −4.85±1.33 log for HCV RNA in sustained responders versus −1.86±1.53 log for others groups, P<0.001. In patients receiving ribavirin in second intention, we also observed a similar drop in HCV RNA and HCV core antigen, predictive of sustained response, −2.67±1.26 log for HCV RNA in sustained responders versus −0.44±0.49 log in non-responders, P<0.001.Conclusions: Ribavirin has probably an additional antiviral effect in interferon treated patients. Kinetics of HCV RNA and HCV core antigen under treatment are highly predictive of a sustained virological response. [Copyright &y& Elsevier]

Abstract Background and Aim: A novel virus, SEN-virus (SENV), was recently discovered. It has been reported as a candidate for a non-A–E hepatitis virus. However, much is still unknown about the clinical significance of SENV. The aim of the present study was to clarify the clinical significance of SENV in patients coinfected with SENV and hepatitis C virus (HCV). Methods: The 52 subjects had chronic hepatitis C and had undergone interferon (IFN) therapy. SEN virus DNA was investigated by using polymerase chain reaction with SENV-specific primers, which we designed to detect all strains of SENV. Additionally, SENV-D and -H were detected by consensus primers. Results: Thirty-five patients were SENV-DNA positive and 22 patients were SENV-D- or -H-positive before IFN therapy. After IFN therapy, in the HCV-RNA eradication group, all cases normalized their serum alanine aminotransferase (ALT). However, in the no eradication group, the ALT no-response rate was 68.7%. In contrast, in the SENV eradication group, the ALT no-response rate was 51.9%, and in the no eradication group, it was 37.5%. Also, in the SENV-D and -H eradication group, the ALT no-response rate was 54.5%, and in the no eradication group, it was 36.4%. The changes in ALT after IFN therapy were significantly correlated with the changes in HCV RNA, but no correlation was found with the SENV DNA presence. Conclusions: Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and SENV appears to primarily be caused by HCV, and is less attributable to SENV. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: Recently, hepatitis C virus (HCV) dynamics during interferon (IFN) therapy have been studied in detail. We examined factors that regulate the viral kinetics and the relationship between the viral kinetics and clinical effect of IFN therapy. Methods: Eighty-eight patients with chronic hepatitis C entered this study. All patients had been treated with 3 MU of IFN-β twice a day for the first 2–4 weeks, then IFN-α for the next 20–22 weeks (three injections per week). The levels of serum HCV RNA were determined by Amplicor HCV Monitor version 1.0, before and 24 h after the first injection of IFN; then the decline of HCV was calculated. Liver inflammation and fibrosis were scored as 0 (none), 1 (mild), 2 (moderate) or 3 (severe) using biopsy specimens. Results: The decline of serum HCV RNA was 1.42 ± 0.65 log copies/mL in genotype 1b and 1.83 ± 0.72 in genotype 2a or 2b (P < 0.01). By a logistic regression model, genotype (1b, 2a or 2b) and hepatic fibrosis (0 or 1, 2 or 3) associated with 24-h decline of serum HCV RNA, independently. As the predictor of IFN therapy, the decline of serum HCV RNA and serum HCV RNA levels before IFN therapy were the independent significant factors ( P < 0.001). Conclusions: The decline of serum HCV RNA during the first 24 h of IFN therapy was regulated by genotypes and hepatic fibrosis. The decline of serum HCV RNA and initial HCV load were independent factors that can be the predictor of the subsequent sustained viral response to IFN therapy. © 2003 Blackwell Publishing Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

Background/Aims: Baseline factors and early decline in serum hepatitis C virus RNA are predictive of sustained virological response to interferon therapy in patients with chronic hepatitis C. We evaluated the prognostic value of baseline factors and early viral RNA among patients treated with peginterferon alfa-2a (40KD).Methods: Data were pooled from three randomized trials involving 814 patients treated with peginterferon alfa-2a (40KD) (90, 135, or 180 μg). Stepwise and multiple logistic regression identified independent baseline factors associated with response. Receiver operating characteristic curves for both absolute values and log10 decline in viral RNA at 4, 8, 12 and 24 weeks of therapy were created.Results: Independent prognostic factors for sustained virological response included viral genotype non-1, low pretreatment viral load, age (<40 years), no cirrhosis and body weight (<85 kg). In addition, alanine aminotransferase quotient (>3) and histological activity index score (>10) were also independently prognostic. Receiver operating characteristic curves showed that detectable or less than 2-log10 decline in viral RNA at week 12 predicted sustained virological non-response (negative predictive value is 98%).Conclusions: In patients with chronic hepatitis C treated with peginterferon alfa-2a (40KD), the decision to continue or stop treatment can be made as early as week 12. [Copyright &y& Elsevier]

Aims: The relationship between the hepatitis G virus (HGV) RNA-positive state or the HGV anti-E2 antibody-positive state, and various clinical parameters among patients with C-viral chronic liver disease and blood donors, was examined. Patients and methods: The subjects consisted of 166 patients with hepatitis C virus (HCV) RNA-positive liver disease, and 157 blood donors. Serum samples were tested for the presence of HGV RNA by the polymerase chain reaction method. The HGV E2 antibody level was measured with an enzyme-linked immunosorbent assay kit. Results: HGV RNA was detected in 1.3% of the blood donors, and HGV E2 antibodies were detected in the sera of 2.5% of the blood donors. The detection rate of HGV RNA and HGV E2 antibodies among the patients with C-viral liver disease was 4.8 and 28.3%, respectively. The detection rates of HGV RNA and HGV E2 antibody among those in each F stage were 0 and 25.0% among those in the F1 stage, 2.6 and 34.2% among those in F2, 11.1 and 27.8% among those in F3, 12.5 and 29.2% among those in F4, and 11.1 and 27.8% among those with hepatocellular carcinoma (HCC). The detection rate of HGV RNA increased with the progression of the F stage and HCC, however, the detection rate of HGV E2 antibody among the four F stages and HCC did not significantly differ. In addition, the clinical parameters and background of those who did or did not have HGV E2 antibodies or HGV RNA, did not significantly differ. Conclusion: HGV exposure may promote the progression of liver fibrosis (F stage) in C-viral liver diseases. [ABSTRACT FROM AUTHOR]

Abstract Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common causes of chronic liver disease, cirrhosis and hepatocellular carcinoma. The influence of HCV infection on the clinicopathological and virological profiles of chronic HBV infection was investigated. Methods: A total of 100 chronic HBV carriers with histopathological diagnoses by liver biopsy were studied. Hepatitis B e antigen (HBeAg) and anti-HCV antibody were tested. Serum HCV-RNA was detected by using a nested reverse transcription–PCR assay. A branched DNA (bDNA) assay was used to detect HBV-DNA and quantitate the serum levels. Results: Eighteen (18%) of 100 patients were positive for anti-HCV and HCV-RNA. Patients with concurrent HCV and HBV infection were significantly older than those without HCV infection (P < 0.05). The positive rates of HBeAg and HBV-DNA as well as the serum levels of HBV-DNA in patients with concurrent HCV and HBV infection were significantly lower than those without concurrent HCV and HBV infection (P < 0.01, P < 0.05, and P < 0.001, respectively). By using multivariate analysis, the factors of seroconversion of HBeAg and decreasing level of HBV-DNA were significantly correlated to concurrent HCV and HBV infection in chronic HBV carriers. The factors of increasing age and concurrent HCV and HBV infection were significantly correlated to seroconversion of HBeAg. Conclusions: The concurrent HCV and HBV infection in chronic HBV carriers might result in a suppression of HBV replication that presented with a lower level of serum HBV-DNA and HBeAg seroconversion. Nevertheless, neither more obvious increase in biochemical parameters nor histopathological progression to more advanced liver diseases was observed. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: Hepatic steatosis is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. Methods: One hundred and six patients were enrolled, and patients with alcoholism or diabetes mellitus were excluded. Clinical, biochemical and virologic data, including HCV genotype and serum HCV-RNA titer and histological findings, were compared between patients with and without hepatic steatosis. Results: Fifty-five (52%) of the 106 patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis had significantly higher mean serum levels of triglyceride and γ-glutamyl transpeptidase, higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCV-RNA titer and HCV genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic score than patients without hepatic steatosis (1.9 ± 1.2 vs 1.3 ± 1.0; P = 0.016). There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation/follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of ≥ 2. Conclusion: It was found that 52% of Chinese patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis were more frequently obese and had more severe hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: The clinical outcomes of adult-acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness. Results: The results showed that a significantly younger age, a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite, a higher mean serum level of alanine transaminase, aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B patients than in those with acute hepatitis C (P < 0.05). There was a significantly higher degree of periportal inflammation and total necro-inflammatory activity in the acute hepatitis B patients (P = 0.002 and 0.049, respectively). Fifteen (68.2%) of the 22 patients with acute hepatitis C had detectable serum HCV-RNA, but only two (14.3%) of the 14 tested patients with acute hepatitis B had detectable serum HBV-DNA, detected by using the branched DNA signal amplification assay. Eighteen (82%) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage (P < 0.001). Conclusion: The manifestations of mild clinical symptoms, lower mean serum transaminases and bilirubin levels, a lesser degree of histological periportal necroinflammation, and more patients with a high circulatory viral load among the acute hepatitis C patients, may lead to more of that group developing chronicity than patients with acute hepatitis B. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: Much is still unknown about the clinical significance of TT virus (TTV), which has been reported as a candidate for non A–G hepatitis virus. The aim of this study was to clarify the clinical significance of TTV in patients coinfected with TTV and hepatitis C virus (HCV). Methods: The 95 subjects studied had chronic hepatitis C (CHC), and underwent interferon (IFN) therapy. TT Virus DNA was detected by using polymerase chain reaction. The nucleotide sequences were determined by using a dideoxy chain termination method. A phylogenetic tree was drawn up by using the neighbor-joining method. Results: TT Virus DNA was detected in 37.9% of patients with the use of an open reading frame 1 (ORF1) primer, and in 88.4% of patients by using a 5′ untranslated region (5′ UTR) primer. Using both sets of primers, no differences were found between TTV-DNA-positive and -negative subjects with CHC in the clinical findings. Serum TTV DNA was eradicated in 30.6% of patients with the ORF1 primer, and in 19.1% of patients with the 5′ UTR primer at 6 months after the cessation of IFN therapy. The levels of TTV DNA before IFN therapy were significantly lower in the viral eradication group than in non-eradication group. The changes in alanine aminotransferase (ALT) concentrations were significantly correlated with changes in HCV-RNA in CHC patients with TTV. Moreover, there was no correlation between the changes in TTV DNA and the course of ALT. Conclusion: Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and TTV appears to primarily be caused by HCV and is less attributable to TTV. [ABSTRACT FROM AUTHOR]

The serum levels of soluble β2-μ-associated and β2-μ-free HLA class I heavy chains were determined in 28 interferon-α nonresponder chronic hepatitis C patients retreated with interferon-α plus ribavirin and in 70 healthy subjects. The baseline levels of β2-μ-associated and β2-μ-free HLA class I heavy chains were significantly higher in patients than in healthy controls (P = 0.001). The levels of β2-μ-associated HLA class I heavy chains significantly increased in responder patients with respect to nonresponders at the third month of treatment (P = 0.03). At the sixth month of treatment and after 6 months of follow up the levels of β2-μ-associated HLA class I heavy chains decreased in responder patients and increased in nonresponders. The levels of β2-μ-free HLA class I heavy chains showed only minor changes during and after treatment. We suggest that the determination of hepatitis C virus RNA levels combined with soluble β2-μ-associated HLA class I heavy chains, as a marker of immune activation, could identify interferon-α non responder chronic hepatitis C patients most likely to respond to a retreatment with interferon-α plus ribavirin. [ABSTRACT FROM AUTHOR]

Liver biopsy specimens of pure autoimmune hepatitis (pAIH), autoimmune forms of chronic hepatitis with positivity for anti-hepatitis C virus (anti-HCV) and negativity for HCV-RNA (cAIH-RNA(–)), autoimmune forms of chronic hepatitis with positivity for anti-HCV and HCV-RNA (cAIH-RNA(+)), and chronic hepatitis C (CHC) were compared histologically and statistically to clarify the histological character of the autoimmune form of chronic hepatitis with HCV infection. The following representative histological features were used to investigate: inflammation, fibrosis, plasma cell infiltration, lymphoid aggregates/follicles, non-suppurative destructive cholangitis, and the shape of the enlarged portal tracts. While a considerable overlap in histological features between the pAIH and cAIH-RNA(–) groups and between the CHC and cAIH-RNA(+) groups was recognized, the overlap between the pAIH and CHC groups was small. Significant differences were found between cAIH-RNA(–) and cAIH-RAN(+) groups, especially in necroinflammatory findings. In conclusion, most cases of cAIH-RNA(–) with histological features similar to those of pAIH were shown to be AIH. The remaining cases might be CHC with subsidence of viral duplication. Conversely, many cases of cAIH-RNA(+) with histological findings similar to those of CHC were shown to be CHC clinically mimicking pAIH. The remaining cases might represent coexistence of pAIH and HCV infection. [ABSTRACT FROM AUTHOR]