Serum Viral Load Research Articles

Baseline cholesterol is associated with the response to antiviral therapy in chronic hepatitis C

Hepatitis C virus (HCV) partially interacts with low-density lipoprotein (LDL) receptors, suggesting a role for lipids in regulating HCV clearance. Our aim was to study if baseline lipids can discriminate responders from non-responders among patients with HCV infection. A total of 109 HCV patients were studied. Laboratory measurements included serum lipids, aminotransferases and viral load, as well as HCV genotype determinations. Responders (n = 53) had significantly higher serum baseline levels of total cholesterol, LDL cholesterol and apolipoprotein B compared to non-responders (n = 56). Multivariate logistic regression analysis showed that a 10 mg/dL increase in total cholesterol was associated with 3.02 higher odds of responding to treatment (95% CI 1.74-5.32, P < 0.001), while a 10 mg/dL increase in apolipoprotein B levels was associated with 1.81 higher odds of responding to treatment (95% CI 1.37-2.54, P < 0.001), after adjustment for age, sex, body mass index (BMI), smoking habits, baseline viral load, liver histology and administration of pegylated interferon. An inverse association between BMI and response to treatment was also evident (adjusted odds ratio 0.73, 95% CI 0.55-0.96; P = 0.03). Baseline serum total cholesterol levels and BMI could be helpful in discriminating responders to antiviral therapy among patients with HCV infection.

Modelling the kinetics of hepatitis C virus RNA decline over 4 weeks of treatment with pegylated interferon α‐2b

Viral kinetic models for hepatitis C virus (HCV) have generally assumed that the effectiveness of therapy in blocking virion production, epsilon, is constant. However, with pegylated interferon alpha-2b (PEG-IFN) given weekly, there are significant changes in drug concentration between doses that may lead to changes in drug effectiveness and viral rebounds towards the end of the dosing interval. Here we investigate the effects of using a model that assumes a constant effectiveness for studies involving PEG-IFN. We simulated PEG-IFN treatment in a population of 294 computer simulated 'patients', each characterized by a different set of pharmacokinetic and pharmacodynamic parameters. We then sampled the simulated treatment data over 4 weeks with a schedule similar to that used in viral kinetic studies, and fitted a viral kinetic model assuming constant drug effectiveness, the CE model, to that data. Although the CE model was able to fit to the data well in most cases, the parameter estimates obtained scattered widely both above and below the true values. Thus, this model is less useful to analyse HCV RNA data during therapy with PEG-IFN than with standard IFN given daily. With PEG-IFN accurate estimation of viral dynamic parameters necessitates concomitant measurements of serum viral load and drug concentration.

Toll-like receptor 7 and 9 expression in peripheral blood mononuclear cells from patients with chronic hepatitis B and related hepatocellular carcinoma

The aim of the present study was to investigate the expression of Toll-like receptors (TLR) 7 and 9 in peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B virus (HBV) infection and related hepatocellular carcinoma. The study group was comprised of 52 patients: 41 with chronic hepatitis B and 11 healthy controls. The protein and mRNA levels of TLR7 and TLR9 were evaluated using real-time PCR, Western blot analysis, and flow cytometry. We also detected the serum viral load of HBV in the patients and analyzed the correlation between HBV-DNA copies and the TLR expression. Our results demonstrated a lower TLR7 expression in all HBV infection groups compared to the controls. We found that HBV infection led to a decreased expression of TLR9 mRNA, but an increased expression of the TLR9 protein compared to the healthy group. The TLR protein levels are related to serum HBV-DNA (P<0.01). There are downregulations of TLR7 expression and TLR9 mRNA in PBMC of HBV-infected patients, but an increased TLR9 expression at the protein level.

Role of hepatitis B virus genotype mixture, subgenotypes C2 and B2 on hepatocellular carcinoma: compared with chronic hepatitis B and asymptomatic carrier state in the same area

The role of genotype mixture and subgenotypes remains controversial in determining the clinical outcome of chronic hepatitis B virus (HBV) infection. We aimed to determine their role on the development and the recurrence of hepatocellular carcinoma (HCC). HBV genotypes, serum viral load and hepatitis B e antigen (HBeAg) seroconversion were determined in 462 HCC patients, 234 chronic hepatitis patients and 425 asymptomatic carriers born in Eastern China. In the 462 HCC patients, 62 (13.4%), 337 (72.9%) and 49 (10.6%) had HBV subgenotype B2, C2 and genotype mixture, respectively. Genotype mixture in HCC patients and hepatitis patients was associated with higher viral load than HBV C2 (P = 0.012, P = 0.000) and more frequent than asymptomatic carriers (P = 0.005, P = 0.000). HBV C2 was more prevalent in HCC patients compared with controls. Proportion of HBV B2 in HCC patients decreased consecutively from <30 to 50-59 years group (P = 0.024). Age-related changes of HBeAg seroconversion were not consistent with serum viral load in HCC patients with HBV B2 and genotype mixture, quite in contrast to hepatitis patients. By multivariate regression analysis, age >or=40 years and serum viral load (>or=10 000 copies/ml) were independently associated with hepatocarcinogenesis, whereas age <or=50 years and HBV B2 were independently associated with HCC recurrence after surgical resection. In conclusion, HBV coinfections with two or three genotypes were associated with higher viral load and more severe course of the disease. HBV B2 infection was related to HCC recurrence. HBV C2 predominance in HCC patients was related to the high prevalence in Eastern China.

Virion half-life in chronic hepatitis B virus infection is strongly correlated with viral load

Little is known about the mechanisms determining clearance rates of hepatitis B virus (HBV) in chronically infected individuals. Mathematical modeling of viral kinetics may reveal new aspects of this disease. During chronic infection, the rates of viral production and clearance are in balance and determine virion half-life. Methods: Using the relationship between intracellular relaxed circular DNA (rcDNA) and extracellular virions in blood, we performed viral dynamic analysis by quantifying viral loads in serum and in the liver of both treatment naïve chronically HBV-infected patients (N=80), and immunodeficient uPA mice (N=7) repopulated with tupaia hepatocytes and infected with woolly monkey (WM) HBV. Results: We show that free virion clearance in chronic HBV infection can be very rapid and is strongly correlated with viral load (p<0.0001, r=0,83): median half-life was 46 minutes for HBeAg-positive individuals harboring median 4,5×107 HBV-DNA copies/ml serum and a remarkably short 150 seconds for HBeAg-negative individuals with significantly lower median serum HBV-DNA levels (6,5×104 HBV-DNA/ml). Virion half-life in high viremic (4,6×108 WMHBV-DNA copies/ml) immunodeficient uPA mice was similar (90 min) to estimates determined in patients with comparable high titers, suggesting that the fast clearance rates of free virions in high viremic chronic carriers are determined by common non-immune specific mechanisms. However, virion half-life in mice was less dependent on viral load, suggesting that immune components can significantly reduce free virion half-life in chronically HBV-infected individuals with low viral loads.

Viral and Host Correlates of Serum Resistin in Simian AIDS

Resistin is an adipocytokine with a proposed dual role in metabolism and inflammation. In light of the ability to promote inflammatory responses, adipocytokines may prove key factors in modulating the host response to HIV. This study utilizes the simian immunodeficiency virus (SIV) model of HIV/AIDS to investigate changes in serum resistin levels following dietary intervention and SIV infection and determine associations with measures of body composition and disease severity. Resistin levels, body composition (n = 34), and insulin resistance (n = 16) were determined in healthy rhesus macaques. A subset of animals (n = 8) was placed on an atherogenic diet (AD) and subsequently inoculated with SIVmac239. Longitudinal measures of serum resistin, cytokines, viral load, lymphocyte subsets, and body composition were obtained. In healthy macaques consuming a standard diet, resistin levels correlated positively with total fat mass (r = 0.49; p < 0.01) and tissue fat percent (r = 0.53; p < 0.01) but failed to associate with measures of insulin resistance. In contrast, a negative correlation was noted between these measures of adiposity and resistin following SIV inoculation (r = -0.27; p < 0.05 and r = -0.24; p < 0.05, respectively). Viral load correlated positively with serum resistin (r = 0.32; p < 0.01). Serum levels of MCP-1 and sTNF RII demonstrated no correlation with resistin in normal animals on a standard diet, while a significant positive correlation was observed following SIV infection (r = 0.52; p < 0.0001 and r = 0.59; p < 0.0001, respectively). Findings indicate a fundamental difference in the relationship between resistin and body composition following SIV infection and suggest that elevations in resistin parallel measures of disease severity including loss of body fat and viral replication.

Changes in peripheral blood leukocyte subpopulations in piglets co-infected experimentally with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) are pathogens, which can significantly affect the swine industry worldwide. Field surveys suggest that simultaneous PRRSV and PCV2 infection is common in pigs. The objective of this study was to measure the changes in peripheral blood leukocyte subpopulations in piglets co-infected experimentally with PRRSV and PCV2, in order to analyze the synergistic influence of co-infection on the immune system. Changes in peripheral blood leukocyte subpopulations were systematically measured by flow cytometry (FCM). The levels of antibodies to PRRSV and PCV2 were detected by indirect Enzyme-Linked ImmunoSorbent Assay (ELISA) and the indirect fluorescent antibody test (IFA), respectively. Serum viral loads were measured using real-time PCR. The results showed that piglets co-infected with PRRSV and PCV2 exhibited slower generation and lower levels of antibodies to PRRSV and PCV2, and increased amounts and a prolonged presence of both PRRSV and PCV2 in serum, in comparison to the piglets infected with either virus alone. The major finding in our study was that the total and differential leukocyte counts, including white blood cells (WBCs), monocytes, granulocytes and lymphocytes (T, B and NK cells, as well as T-cell subpopulations), dramatically decreased early during co-infection with PRRSV and PCV2 for about two weeks, in contrast with animals singly infected with either PRRSV or PCV2. These results suggest that PRRSV and PCV2 co-infection results in a synergistic decrease in immune cells in the peripheral blood of piglets. These data contribute to the understanding of the immunosuppressive effects resulting from PRRSV and PCV2 co-infection in pigs.

Viral load as predictor of Crimean-Congo hemorrhagic fever outcome.

We used quantitative real-time reverse transcription–PCR to measure viral load in serum from 24 patients in Kosovo who had acute Crimean-Congo hemorrhagic fever. Viral load correlated with clinical disease and antibodies and could be used as a predictor of disease outcome.

Circulating CD4+ CD25+ regulatory T cells correlate with chronic hepatitis B infection.

Circulating CD4+ CD25+ regulatory T cells (Tregs) have been demonstrated to maintain immunotolerance and suppress the antigen-specific or antigen-non-specific T-cell responses, but their role in chronic hepatitis B (CHB) infection in humans has not been well characterized. In this study, we analysed the frequency and phenotypic characteristics of CD4+ CD25+ Tregs in patients of different hepatitis B virus (HBV) infection status, and investigated the effect of Tregs on antiviral immune responses in CHB patients, and the mechanism of this effect. A total of 137 subjects, including 79 CHB patients, 26 asymptomatic HBV carriers (ASCs), 12 acute hepatitis B (AHB) patients and 20 healthy controls, were enrolled in the study. We found that the frequency of CD4+ CD25(high) Tregs in AHB patients was comparable to that in healthy controls, while it was significantly increased in CHB patients. CD4+ CD25+ Tregs produced interleukin (IL)-10 but little or no interferon (IFN)-gamma under anti-CD3 stimulation. In CHB patients, the frequency of CD4+ CD25(high) Tregs positively correlated with serum viral load, and the Tregs were capable of suppressing the proliferation and IFN-gamma production of autologous peripheral blood mononuclear cells (PBMC) mediated by HBV antigen stimulation in vitro. However, combined administration of anti-programmed death-1 (PD-1) and anti-cytotoxic lymphocyte antigen-4 (CTLA-4) monoclonal antibody slightly enhanced the cellular proliferation and significantly increased the IFN-gamma production of PBMC cocultured with Tregs at a ratio of 2:1. Thus, the frequency of circulating CD4+ CD25+ Tregs is increased in patients with CHB, and this may play an important role in viral persistence by modulating virus-specific immune responses.

Kaposi’s sarcoma herpesvirus load in biopsies of cutaneous and oral Kaposi’s sarcoma lesions

Objectives To evaluate human herpesvirus 8/Kaposi’s sarcoma associated herpesvirus (HHV-8/KSHV) viral load in diagnostic, (formalin fixed, paraffinised) biopsies and patient serum during tumour progression of oral and cutaneous AIDS-related Kaposi’s sarcoma (AKS), and endemic Kaposi’s sarcoma (EKS) by a sensitive and specific quantitative real time polymerase chain reaction (qRT-PCR) assay. Study design Eighty six biopsies of both AKS (oral and cutaneous AKS, 68) and EKS (cutaneous EKS, 18) were evaluated by qRT-PCR and immunohistochemistry (IHC). The viral load in human tumour tissue and serum of some individual patients were compared. Results Higher viral load as well as frequency of latency-associated nuclear antigen (LANA)+ tumour spindle cells (SC) and number of LANA granules per SC was found in oral AKS compared to cutaneous AKS. Although few cases were available, serum viral load appeared to decrease compared to tumour tissue during KS progression. Conclusions The higher viral load in oral rather than cutaneous AKS is consistent with the well recognised reservoir function of the oral mucosa. Decrease of serum HHV-8 load during KS progression may indicate decreased virus release and/or increased virus clearance.

HIV-1 RNA concentration and cognitive performance in a cohort of HIV-positive people

To determine whether higher viral concentrations in the cerebrospinal fluid (CSF) and/or peripheral blood were associated with greater severity of cognitive impairment in HIV-1-seropositive subjects with cognitive-motor impairment. Cognitive performance measurements and viral load were obtained from HIV-1-seropositive individuals with cognitive-motor impairment entering a clinical trial before the introduction of highly active antiretroviral therapy (HAART). CSF viral load (UltraSensitive Roche HIV-1 Monitor test with detection limit of 50 copies/ml) was available from 179 patients, and peripheral (plasma or serum) viral load from 111 patients. Of these patients, 62% met the 1993 Centers for Disease Control (CDC) criteria for AIDS, and 19% had clinically significant cognitive impairment (i.e., global deficit score > or = 0.5). Possible associations between viral load and cognitive scores were examined with general linear regression models with and without adjustment for age, education, study site, antiretroviral use, CD4 cell count, and CDC stage. The mean CSF viral load was 2.83 log(10)/ml +/- 0.94 (SD) (undetectable in 19.5%). Mean peripheral viral load was 4.11 log(10)/ml +/- 0.90 (SD). No statistically significant associations emerged between either CSF or peripheral viral load and the global deficit score, or any of the seven cognitive domain deficit scores. Among these HIV-1-sero-positive individuals with mainly minor HIV-1-associated cognitive deficits and not receiving HAART, no association between CSF or blood concentration of HIV-1 RNA and cognitive performance could be found. These results suggest that the severity of HIV-1-associated cognitive impairment is not directly related to concurrent viral concentration in the CSF or the peripheral blood.

Detection of neutralizing antibodies in postweaning multisystemic wasting syndrome (PMWS)-affected and non-PMWS-affected pigs

The notion that postweaning multisystemic wasting syndrome (PMWS)-affected pigs develop an impaired humoral response against porcine circovirus type 2 (PCV2) has been reported in several studies. However, little information is available regarding the presence of neutralizing antibodies (NA) in PCV2-infected pigs and their role in the pathogenesis of the disease. The aim of the present work was to further characterize the humoral response, and in particular the production of NA, in pigs with different PCV2-infection status. Seventy-two conventional pigs from different farms were classified into three groups based on PCV2 infection and clinico-pathological status, namely: PCV2-negative, non-PMWS PCV2-positive and PMWS-affected animals. In addition, 9-week old pigs from an experimental infection (6 controls and 14 PCV2-inoculated pigs) were also studied. NA and total PCV2 antibodies (TA) as well as viral load in serum were determined and correlated with the clinico-pathological status of pigs. Results indicated that PMWS-affected pigs had lower NA titres, if any, than healthy animals. NA titres were also inversely correlated with PCV2 load in serum. NA and TA titres were positively correlated; however, correlation differed among infection status, being lower in PCV2-positive pigs. Also, the diagnostic performance of each test was evaluated, indicating that the combination of viral neutralization and quantitative PCR in serum was useful to discard PMWS (specificity 92%). In experimentally infected animals, the evolution of NA paralleled the course TA, although a slight delay in NA production was seen in some animals. The increase of NA coincided with the drop in viral load. Results from this work further support that PMWS-affected pigs show an impaired humoral immune response and, particularly, an inefficient NA response against PCV2.

Non-relationship between HCV genotype, serum viral load, and ALT, AST levels in chronic hepatitis C patients

目的 研究HCV基因型、RNA含量与肝损伤指标的相关性.方法 对来自14家医院的208例慢性丙型肝炎患者的血清进行ALT、AST检测,采用罗氏公司的Cobas Amplicor HCV Monitor Test version 2.0(v2.0)试剂进行HCV RNA定量和Simmons酶切分型方法进行HCV基因分型检测,分析HCV基因型、HCV RNA含量与ALT、AST水平及AST/ALT比值的相关性.结果 本研究的208例慢性丙型肝炎患者中,基础HCV RNA含量与ALT、AST水平及AST/ALT比值没有相关性(r值分别为0.093、0.092、0.009,均P＞0.05),高病毒含量组(≥8.5×105 IU/ml)与低病毒含量组(＜8.5×105IU/ml)比较ALT、AST水平及AST/ALT比值的差异无统计学意义(P=0.101、0.052、0.746);HCV基因1型与非基因1型之间ALT、AST、AST/ALT的差异无统计学意义(P=0.406、0.461、0.528),HCV基因1型与非基因1型之间RNA含量差异无统计学意义(P＞0.05);治疗结束时病毒应答组和非应答组比较的ALT、AST水平及AST/ALT比值的差异无统计学意义(P=0.443、0.641、0.942),随访结束时,病毒应答组和非应答组的ALT、AST水平及AST/ALT比值的差异无统计学意义(P=0.201、0.411、0.76).结论 慢性丙型肝炎患者的HCV基因型和RNA病毒含量与肝损伤指标没有相关性。

Early Virological Response in Children with Chronic Hepatitis C Treated with Pegylated Interferon and Ribavirin

Infection with hepatitis C virus (HCV) is widespread worldwide. It is estimated that this problem affects approximately 3% of global population. By introducing weekly doses of pegylated interferon (IFN) alfa in combination with ribavirin, given daily, to chronic hepatitis C (CHC) treatment one can achieve a full inhibition of HCV replication in 54-56% of adult patients. The aim of this study was to examine the relationship between prognostic factors and early virological response (EVR) after combination treatment with peginterferon alfa- 2a or alfa-2b and ribavirin in children with CHC. Twenty-three children with chronic HCV were treated with a combination of peginterferon alfa-2a or alfa-2b once a week and ribavirin twice a day. Assessment included age at the time of infection, the length of infection, HCV genotype, viral load in serum and HCV RNA level in peripheral blood mononuclear cells (PBMCs), alanine aminotransferase (ALT) activity and adherence to therapy. The efficacy endpoint was EVR defined as undetectable HCV RNA in serum or >2 log10 decrease in HCV RNA compared with baseline values. An EVR was achieved in 15 out of 23 patients (65.3%) after 12 weeks of therapy. Lower HCV RNA viral load have positive influence on EVR. HCV RNA presence in PBMCs and lower ALT activity do not influence the achievement of EVR. Oncologic history does not bear any influence on EVR. Adherence to the therapy has an unclear influence on the achievement of EVR in children with CHC.

Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy

Given that highly active antiretroviral therapy (HAART) has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1)-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI) antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40) against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

Poly(I:C) and Lipopolysaccharide Innate Sensing Functions of Circulating Human Myeloid Dendritic Cells Are Affected In Vivo in Hepatitis C Virus-Infected Patients

The role of peripheral dendritic cells (DCs) in hepatitis C virus (HCV) infection is unclear. To determine if persistent infection exerts an inhibitory pressure on HCV-specific innate responses, we analyzed DC function in blood through quantification of cell-associated HCV RNA levels in conjunction with multiparametric flow cytometry analysis of pathogen recognition receptor-induced cytokine expression. Independently of the serum viral load, fluorescence-activated cell sorter-purified total DCs had a wide range of cell-associated HCV genomic RNA copy numbers (mean log(10), 5.0 per 10(6) cells; range, 4.3 to 5.8). Here we report that for viremic patients with high viral loads in their total DCs, the myeloid DC (MDC) subset displayed impaired expression of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) but normal IL-6 or chemokine CCL3 expression in response to poly(I:C) and lipopolysaccharide (LPS). IL-6-expressing cells from this subgroup of viremic patients demonstrated a significant increase (sixfold more) in TNF-alpha(-) IL-12(-) cell frequency compared to healthy donors (mean, 38.8% versus 6.5%; P < 0.0001), indicating a functional defect in a subpopulation of cytokine-producing MDCs ( approximately 6% of MDCs). Attenuation of poly(I:C) and LPS innate sensing was HCV RNA density dependent and did not correlate with viremia or deficits in circulating MDC frequencies in HCV-infected patients. Monocytes from these patients were functionally intact, responding normally on a per-cell basis following stimulation, independent of cell-associated HCV RNA levels. Taken together, these data indicate that detection of HCV genomic RNA in DCs and loss of function in the danger signal responsiveness of a small proportion of DCs in vivo are interrelated rather than independent phenomena.

Influence of etanercept on serum liver related tests and viral load values in patients with psoriasis and hepatitis C infection

Influence of etanercept on serum liver related tests and viral load values in patients with psoriasis and hepatitis C infection

The High Incidence of the Emergence of Entecavir-Resistant Mutants among Patients Infected with Lamivudine-Resistant Hepatitis B Virus

Hepatitis B virus (HBV) infection remains to be one of the most prevailing infection in the world, causing chronic liver diseases. Although lamivudine has been effective to suppress HBV replication, longer durations of administration can lead to the emergence of drug-resistant mutant viruses, followed by reactivation of hepatic inflammation (breakthrough hepatitis). Moreover, the optimal period of administration as well as the effects of anti-viral nucleot(s)ide such as lamivudine, adefovir, and entecavir, has not been established. To evaluate the efficacy of the anti-viral effects of entecavir for lamivudine-resistant HBV, we administered entecavir sequentially in four patients with chronic HBV infection, who demonstrated the emergence of lamivudine-resistant HBV and histological active hepatitis. The antiviral effects were evaluated by the serum viral loads and biochemical laboratory data. After follow-up periods of more than 36 months, we found high incidence in the emergence of entecavir resistant mutants (3/4, i.e., 75%). An additional mutation at the 184th amino acid, different from the previously reported lamivudine-resistant mutations (80th, 180th, and 204th), seemed to have a close relationship with the induction of entecavir-resistant mutants at least for Japanese HBV genotype C. Our observation draws attention to the possibility that the usage of entecavir for lamivudine-resistant HBV could promptly induce entecavir-resistant mutations in addition to lamivudine-resistance.

Sustained Virological Response Rate and Host Background in Chronic Hepatitis C Patients Receiving Various Interferon Therapies

BACKGROUND/AIM: To determine the sustained viral response (SVR) rate and to investigate the baseline host and viral characteristics of chronic hepatitis C (CHC) patients who achieved an SVR with interferon (IFN) alone or IFN plus ribavirin. PATIENTS AND METHODS: One hundred and forty-seven adults with CHC were studied. Baseline serum HCV-RNA was quantified by RT-PCR, and the HCV serotype was classified as S1 and S2. IFN therapy was selected according to the serum HCV-RNA load: IFN-alpha 2b plus ribavirin were given to 63 patients, while the other 84 patients were treated with IFN alone (53 patients received IFN-alpha or -alpha 2b, and 31 patients received consensus IFN). All IFNs were administered daily for 2 weeks, followed by the same dose thrice weekly for a median of 22 weeks (14-94 weeks). Twenty-four weeks after finishing therapy, SVR was defined as negative serum HCV-RNA by a qualitative PCR, and patients with any other outcome were defined as nonresponders. Peripheral blood CD4 positive T cell subsets (Th1 and Th2 cells), NK cells, serum cytokines, and standard liver function tests were measured before starting therapy. RESULTS: An SVR was achieved in 87 patients, while 60 patients were nonresponders. Multiple logistic regression analysis revealed that the serum log 10-transformed HCV-RNA load, serotype, and liver fibrosis were independent factors for SVR. According to univariate logistic regression analysis, serum Log IL-10 and peripheral blood Th1 cells were significant predictors of SVR. CONCLUSION: Our results suggest that an SVR is strongly associated with S2, serum HCV-RNA load, and mild fibrosis, even when therapy is chosen according the serum viral load and serotype. Rec.11/17/2006, Acc.11/27/2006, pp187-193

Early HBV DNA suppression in serum as predictive marker of long-term antiviral efficacy

Background and aims: As reported previously (Wursthorn et al, Hepatology 2006; 44: 675–84) 48 weeks of combination therapy with PEG-IFN alfa–2b and Adefovir (ADV) in patients chronically infected with Hepatitis B Virus (HBV) led to reduction of intrahepatocellular cccDNA by –2.4 log and was accompanied by high numbers of HBsAg seroconversion (4/24 patients) and HBeAg loss or HBeAg seroconversion (8/15 HBeAg-positive patients). Maximal early reduction of serum viral load has been associated with improved treatment outcomes and less resistance in HBV patients. The aim of this study was to link early virological response at weeks 4, 8, and 12 and subsequent virological and clinical efficacy. Methods: 26 patients received a 48 weeks course of 12kDa pegylated interferon alpha 2b 1.5µg/kg bw qw and ADV 10mg qd followed by 48 weeks of ADV 10mg qd. HBV-DNA in serum was quantified in four week intervals and viral response was defined as serum HBV-DNA by pcr below detection limit (LLoD=100 copies/ml). Results: Clinical and virological efficacy responses at one and two years of antiviral treatment were proportional to early viral responses. After 48 and 96 weeks of therapy serum HBV-DNA was undetectable in 14/24 patients (58%). Positive predictive values (PPV) at week 4/8/12 predicting viral response both at week 48 and 96, were 100% (5/5); 91% (10/11); 64% (9/14), respectively. Furthermore, we found that patients with detectable HBV DNA in the first 8 weeks of combination therapy had >80% probability (negative predictive value: NPV; specificity=86%, sensitivity=90%) of not achieving long-term viral response. Interestingly, all patients (4/4) who developed antiHBs antibodies became HBV DNA negative within the first 8weeks of therapy. Conclusion: Suppression of serum HBV DNA levels below LLoD within the first 8 weeks of combination therapy was strongly associated with long-lasting antiviral efficacy in patients receiving combination therapy with PEG-IFN and NA, indicating that early measurement of HBV DNA kinetics is a valuable prognostic marker of long-term viral response and may be useful in optimising patient management.