Low HCV RNA Levels Research Articles

Thiol-disulphide balance and total oxidant-antioxidant status in patients with chronic hepatitis C.

To assess the dynamic thiol/disulphide homeostasis (DTDH) and total oxidant/antioxidant status in patients with hepatitis C virus (HCV) infection and to evaluate their association with HCV-RNA levels. Levels of serum total thiol (TT), native thiol (NT), disulphide (DS), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) as oxidative stress markers were determined in 162 individuals, including 74 patients with HCV infection and 88 non-HCV controls. HCV genotypes and HCV-RNA levels of the patients were recorded. The NT, TT and TAS levels and NT/TT ratio were significantly lower in the HCV group compared with the control group. On the contrary, DS, TOS and OSI levels and DS/NT and DS/TT ratios were significantly higher. Patients with high HCV RNA levels (> 650000IU/mL) had higher DS levels than patients with low HCV-RNA levels (<650000IU/mL). Genotype 1 was observed in 68.9% of patients with HCV. Levels of oxidative stress parameters were similar between genotype 1 and other genotypes (2, 3 and 5). No significant correlations were found between oxidative stress markers and albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin and HCV-RNA levels in patients with HCV infection. A negative correlation was found only between OSI and albumin. Our results suggest that DTDH shifts towards the DS direction because of thiol oxidation in HCV-infected patients. Furthermore, DS levels were significantly higher in patients with high HCV-RNA levels compared with patients with low HCV-RNA levels.

Ribavirin facilitates early viral kinetics in chronic hepatitis C patients receiving daclatasvir/asunaprevir.

Ribavirin (RBV) remains crucial in difficult-to-cure chronic hepatitis C patients receiving directly acting antivirals (DAAs). The current study aimed to address whether RBV enhanced early viral kinetics in patients with DAAs. Hepatitis C virus (HCV) genotype-1b patients were allocated to daclatasvir/asunaprevir +weight-based RBV (1000-1200mg/day) for 12-24weeks. HCV RNA levels were compared at day 1, week 1, week 2, and week 4 of treatment. The sustained virological response rate was 100% (67/67) and 96.7% (59/61) in the RBV and non-RBV group, respectively. The HCV RNA levels at treatment week 2 (W2) were significantly lower in the RBV group than in the non-RBV group (0.42±0.81 log IU/mL vs 0.79±1.03 log IU/mL, P=0.04). Among the intermediate responders who remained to have detectable RNA after W1 of treatment, patients with RBV had a significantly higher rate of undetectable HCV RNA (71.4% vs 36.0%, P=0.003) and lower HCV RNA level at W2 (0.55±0.89 log IU/mL vs 1.32±1.04 log IU/mL, P=0.001). A more significant magnitude of HCV RNA reduction was also noted from baseline to day 1 (3.15±0.38 log IU/mL vs 2.80±0.70 log IU/mL, P=0.009) and W1 to W2 (1.40±0.65 log IU/mL vs 0.88±0.78 log IU/mL, P=0.007) in the RBV group compared to the non-RBV group among the intermediate responders. Logistic regression analysis revealed that adding RBV independently predicted undetectable HCV RNA at W2 (odds ratio/confidence interval: 4.74/1.54-14.57, P=0.007) in the intermediate responders. Adding RBV to DAAs improved early viral kinetic, in particular, for intermediate responders.

Community screening for hepatitis C virus infection in a low-prevalence population

BackgroundAge cohort screening for hepatitis C virus (HCV) might be an effective strategy if the majority of undiagnosed cases are concentrated in a particular age group. The objective of this study was to determine HCV prevalence in different age cohorts of the general population in the Central European part of Russia and second, to assess feasibility of HCV antigen testing for community screening programs.MethodsSera from 2027 volunteers were tested for anti-HCV (Architect Anti-HCV, Abbott Laboratories). All anti-HCV reactive samples were confirmed in an immunoblot and tested for HCV Ag (ARCHITECT HCV Ag, Abbott Laboratories), HCV RNA and HCV viral load.ResultsOut of 31 individuals with anti-HCV reactive result, 22 (71%) were confirmed by immunoblot, six were false positives and three were indeterminate. Active infection was observed in 73% of anti-HCV confirmed positives. Five out of 16 individuals had low HCV-RNA levels (< 10,000 IU/mL) and one of those had a very low level (594 IU/mL). Agreement between HCV Ag and HCV RNA was 100%. Total anti-HCV and active HCV infection rates were 1.09% (22/2027) and 0.79% (16/2027), respectively. The peak rates were observed in people 60 years or older (anti-HCV: 2.84% [95% CI: 1.66–4.74%], 13/319; HCV RNA/HCV Ag: 2.23% [95% CI: 1.20–4.00%], 10/319).ConclusionsOverall HCV prevalence is low, except in people 60 years or older. The latter should be considered as a target group for HCV screening. The high agreement between HCV RNA and HCV Ag suggests the utility of HCV Ag testing to confirm active infection in screening programs.

Efficacy of direct-acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study.

Although the development of new direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection has markedly advanced, the effects of cirrhosis on DAA treatment remain unclear. We aimed to clarify the impact of cirrhosis on DAA treatment of patients infected with HCV. This large-scale, multicenter, retrospective study consisted of 2130 HCV genotype 1b-infected patients who were treated with one of the following DAA combination therapies: asunaprevir/daclatasvir (ASV/DCV), ledipasvir/sofosbuvir (LDV/SOF), or paritaprevir/ombitasvir/ritonavir (PTV/OBV/r). Ninety-two patients (4.3%) previously received DAA-based treatment. Seven hundred and forty-five patients (34.9%) had cirrhosis. Overall, the sustained virologic response (SVR) rate was 93.0%. The SVR rates in patients who received ASV/DCV, LDV/SOF, or PTV/OBV/r were 90.0%, 96.9%, and 97.6%, respectively. The SVR rate in patients with cirrhosis (89.1%) was significantly lower than that in patients without cirrhosis (95.1%, P = 6.94 × 10-7 ). In the multivariate analysis for the overall cohort, absence of cirrhosis (P = 1.26 × 10-3 ), no previous DAA-based treatment (P = 2.54 × 10-14 ), low HCV-RNA levels (P = 1.64 × 10-6 ), wild-type non-structural protein 5A L31/Y93 (P = 7.33 × 10-13 ), and DAA regimen (LDV/SOF or PTV/OBV/r) (P = 1.92 × 10-14 ) were independent factors contributing to SVR. Except for patients with DAA-based treatment history, absence of cirrhosis (P = 2.15 × 10-3 ; odds ratio, 2.51) was an independent factor contributing to SVR in 2038 DAA-naïve patients. This study suggests that the presence of cirrhosis reduces the SVR rate of DAA treatment, regardless of the type of DAA treatment.

Inflammatory Biomarkers and Liver Histopathology in Non-Uremic and Uremic Chronic Hepatitis C Patients

The aim of this study is to investigate the association between hepatic activity index (HAI) and fibrosis score (FS) with inflammation biomarkers in non-uremic and uremic hepatitis C positive patients. Fifty chronic hepatitis C (cHepC) positive patients, having a liver biopsy were included in this study. Liver biopsies were scored according to modified ISHAC scoring system. 25 healthy controls of similar age and gender were also enrolled as control group. Serum YKL-40, neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (PLR), CRP and Immunoglobulin (IgG, A and M) levels were used to determine inflammation. AST to Platelet Ratio Index (APRI) score was also evaluated. According to biopsy findings patients were divided into 2 groups: low (0-2) and severe (3-6) FS. Patients with cHepC had increased inflammation compared to the healthy controls. End-stage renal disease (ESRD) patients had higher levels of inflammation markers (NLR, IgG, CRP and YKL-40) and lower HCV RNA levels, HAI and FS compared to non-uremic patients. When patients were grouped into 2 according to FS as mild and severe, IgG (p < 0.001), YKL-40 (p = 0.02) levels and APRI score (p = 0.002) were significantly higher compared to mild FS (p = 0.002). YKL-40 levels (t value: 3.48; p = 0.001) and APRI score (t value: 4.57, p < 0.001) were found as independent associated with FS in non-uremic patients. However, in adjusted models, only APRI score (t value: 3.98, p = 0.002) was an independent associated with FS in ESRD patients. In non-uremic cHepC patients, YKL-40 levels and APRI score may be valuable markers of FS. In ESRD patients, there is not sufficient data for prediction of HAI and FS. In these patients, APRI score may provide better information.

Evaluation of Resistance-Associated Substitutions in NS5A Using Direct Sequence and Cycleave Method and Treatment Outcome with Daclatasvir and Asunaprevir for Chronic Hepatitis C Genotype 1.

BackgroundThe aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants.MethodsA total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated.ResultsOverall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80%-30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR.ConclusionNS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination.

TG1050, a novel immunotherapeutic for the treatment of chronic hepatitis B, can control HBsAg and provoke HBsAg seroconversion in HBV-persistent mouse models

s / Journal of Clinical Virology 69 (2015) 223–246 227 evaluated with serial dilutions (106–100 IU/mL; Roche). The quantitative correlation and lower limit of detection were evaluated by use of clinical samples. Findings: Picodroplet digital PCR showed a high degree of linearity (R2 =0.9891) and accuracy (SD≤0.31 log copies/mL; CV≤15%) across their detectable ranges. The quantitative correlation between the picodroplet digital PCR and the Roche TaqMan HCV test was high (R2 =0.9439) across their detectable ranges (106–15 IU/mL). We also found discordance in detection of low HCVRNA samples between the twomethods. In 18 clinical samples (HCV RNA 15 copies/mL, 44.4% with an HCV RNA levels < 15 copies/mL, and in 33.3% of samples the target was not detected. The discordance in low RNA samples needs to be verified using a large sample size. Interpretation: Picodroplet digital PCR could provide a useful method for HCV quantification, especially for low HCV RNA levels, but the approach needs to be further optimised. http://dx.doi.org/10.1016/j.jcv.2015.06.018

The Association of HLA Class II Alleles with the Response to Alfa-Interferon/Ribavirin Therapy in Chronic Hepatitis C Patients

Human Leucocyte Antigens (HLA) class II appears to play an important role in the individual’s immune response to viral infection. The present study was aimed at assessment of the relationship between HLA DRB1 alleles and the response to HCV combined therapy in Chronic Hepatitis C patients (CHC). We enrolled a total of 44 chronically infected HCV patients without Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV). Their mean age was 36.45±11.18 years (21-63). HLA-DRB1 typing was done by real time Polymerase Chain Reaction (PCR). ALT and Hemoglobin (Hb) levels were assessed as well as viral genotype was taken from patients' reports (HCV genotypes were 1, 2, 3 and 4 representing 13.6, 13.6, 4.5 and 68.18%, respectively). The most frequent alleles demonstrated among patients were DRB1*13 and DRB1*07 (31.8 and 36.4%, respectively). Analysis of DRB1 frequency between sustained responders and non responders revealed that DRB1*13 allele was significantly higher among sustained responders (p<0.001), while DRB1*07 allele was significantly higher among non responders (p<0.01). Female sex, HCV genotype 2 and pretreatment low serum HCV RNA level were associated with Sustained Virological Response (SVR). Also, elevated Alanine aminotransferase (ALT) level at the 1st week of therapy followed by return to baseline level at the 4th week and a decrease of the mean hemoglobin concentration at 4th week and 12th week of therapy were significantly associated with SVR. We concluded that the virological and special HLA patterns may possibly predict the response to combination therapy in CHC patients.

Lower incidence of hepatocellular carcinoma and cirrhosis in hepatitis C patients with sustained virological response by pegylated interferon and ribavirin.

To elucidate the benefits of successful antiviral therapy in chronic hepatitis C (CHC) patients A total of 463 CHC patients who underwent pegylated interferon alfa and ribavirin therapy were classified as sustained virological response (SVR) or non-SVR based on response to antiviral therapy. We investigated disease progression to cirrhosis in non-cirrhotic patients, development of cirrhosis-related complications such as ascites, variceal bleeding, and hepatic encephalopathy in patients with cirrhosis, and development of hepatocellular carcinoma (HCC). Three hundred patients achieved SVR, and 163 were classified into the non-SVR group. The overall SVR rates were 64.8 %, and multivariate analysis showed that younger age, non-cirrhosis, HCV genotype 2 or 3, lower HCV RNA level (<800,000 IU/mL), and lower body weight were independent factors associated with SVR (all P < 0.05). During a median follow-up of 36.1 months, non-cirrhotic patients with SVR had significantly lower risk of progression to cirrhosis compared with patients with non-SVR (P < 0.001). Moreover, SVR was related to a reduced risk of HCC development (P = 0.017). SVR resulted in significantly more favorable long-term outcomes, such as lower risk of progression to cirrhosis and HCC occurrence compared with non-SVR.

Sustained Virological Response Rates to Antiviral Therapy in Genotype 1 and 3 Chronic Hepatitis C Patients: A Study from North India

In India, both genotype 3 and 1 are predominant genotypes in patients with chronic hepatitis C (CHC). However, there is scanty data on sustained viral response (SVR) rate with conventionally recommended dual therapy with PEG-IFN and ribavirin. In this retrospective study, consecutive patients of CHC of genotypes 1 and 3, attending the single unit of Gastroenterology of our hospital, who received PEG-IFN and ribavirin therapy, were included. Patients who had co-infection with HIV or HBV were excluded. A total of 114 patients were included in the study median age 44 (15-72) years, 79% males. Most common presentation was with chronic hepatitis, while 10 (9%) patients had compensated cirrhosis. Nine (8%) patients had associated diabetes, 16 (14%) patients gave history of significant alcohol abuse. The median baseline HCV RNA level was 3.0×10(5) (1.7×10(3)-1.8×10(7))IU/mL. The most common genotype was 3 (75%) followed by genotype 1 (25%). 70% patients received PegIFN-α2a (median dose 180MIU/wk) and 30% patients received PegIFN-α2b (median dose 80MIU/wk). The median ribavirin dose was 800 (range 800-1200)mg. SVR in genotype 1 was 64% (18/28) while SVR in genotype 3 was 73% (63/86). The factors predicting SVR on univariate analysis were a lower baseline HCV RNA level (less than 3.0×10(5)), higher hemoglobin level>11.8g/dl, and achievement of rapid virological response (RVR), early virological response (EVR) and end of treatment response (ETR). In multivariate analysis the only baseline factor found independently correlating with SVR was low HCV RNA level (<3.0×10(5)IU/mL) (P=0.003). In north India, HCV genotype 3 has a SVR rate of 73%, which is comparable to genotype 1 with SVR rate of 64% when treated with PEG-IFN and ribavirin therapy. A baseline HCV RNA level lower than 3.0×10(5) best predicts SVR in addition to achievement of RVR, EVR or ETR.

Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression.

To evaluate steatosis, insulin resistance (IR) and patatin-like phospholipase domain-containing 3 (PNPLA3) and their relation to disease progression in hepatitis B and C viruses (HCV-HBV) co-infected patients. Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled: 66 had HBV-HCV, 66 HBV and 198 HCV infection. Prevalence of steatosis, IR and PNPLA3 polymorphisms and their relation to anthropometric, biochemical, virological and histological parameters were evaluated. Prevalence of steatosis in group HBV-HCV was similar to that in HCV (47.0% vs 49.5%, respectively); group HBV showed the lowest steatosis (33.3%). Group HBV-HCV had a lesser degree of steatosis than HCV (P = 0.016), lower HCV RNA levels (P = 0.025) and lower prevalence and degree of IR (P = 0.01). PNPLA3 polymorphisms were associated with steatosis. Group HBV-HCV showed higher levels of liver fibrosis than group HCV (P = 0.001), but similar to that observed in HBV group. In HBV-HCV group, liver fibrosis was not associated with steatosis, IR or PNPLA3. HBV infection was the independent predictor of advanced liver fibrosis. HBV-HCV co-infected patients have lower degree of hepatic steatosis, IR and HCV RNA than HCV mono-infected; co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.

Role of Interleukin 28B-related Gene Polymorphisms in Chronic Hepatitis C and the Response to Antiviral Therapy in Koreans

Genetic variations in interleukin 28B (IL28B) have been strongly associated with a sustained virological response (SVR) in European and African-American patients. Genetic variation of IL28B was investigated in healthy controls and chronic hepatitis C (CHC) patients, and the treatment response in the CHC patients was analyzed according to IL28B polymorphism in the Korean population. IL28B polymorphisms (rs12979860 and rs8099917) were studied in 200 healthy controls and in 167 CHC patients who were treated with peginterferon-α and ribavirin. The prevalence of rs12979860 in healthy controls is as follows: the CC-genotype was 88.5%, the CT-genotype was 11.5%, and the TT-genotype was not found. The prevalence of rs8099917 in healthy controls is as follows: the TT-genotype was 89.5%, the TG-genotype was 10.5%, and the GG-genotype was not found. The CC-genotype of rs12979860 and the TT-genotype of rs8099917 were found to be closely related (linkage disequilibrium; D'=1.0, χ =0.9082). In 106 CHC patients treated with peginterferon and ribavirin, the SVR was 67.2% (n=58) for 1b, 91.6% (n=47) for 2a. In hepatitis C virus (HCV) genotype 1b with respect to rs12979860, the SVR in CC-genotype was 72.9% and that in CT-genotype was 40.0%. On investigating predictive factors for SVR, pretreatment low-HCV RNA levels, HCV genotype non-1, early virological response, and also the IL28B CC-genotype for rs12979860 were good indicators of an SVR. In Korea, genetic variation of IL28B is different from that in western countries in view of high prevalence of rs12979860 CC-genotype. It seems likely that a high SVR in Korean patients with genotype 1 CHC patients is due to the genetic polymorphism in IL28B.

Progression of Liver Diseases

Abstract This article does not have abstract.

Intravenous Silibinin as ‘Rescue Treatment’ for On-Treatment Non-Responders to Pegylated Interferon/Ribavirin Combination Therapy

Intravenous silibinin (ivSIL) is a potent antiviral agent against HCV. In vitro silibinin (SIL) inhibits viral replication, possibly by inhibiting HCV RNA polymerase. In this proof-of-concept study, ivSIL was tested in on-treatment non-responders to full-dose of pegylated interferon-α2a/ribavirin (standard of care [SOC]). A total of 27 treatment-naive patients with <2 log drop in viral load after 12 weeks or still detectable HCV RNA after 24 weeks of SOC treatment (mean age 54.4 ±6.8 years, male/female 19/8, HCV genotype 1 n=19, 3a n=4 and 4 n=4, liver fibrosis F4 n=14, F3 n=5 and F2 n=3, and interleukin 28B polymorphism C/C n=1, T/C n=22 and T/T n=4) received additionally 20 mg/kg/day SIL (Legalon-SIL(®); Rottapharm-Madaus, Monza, Italy) intravenously for 14 or 21 days. Thereafter, pegylated interferon/ribavirin was continued. HCV RNA was quantified by TaqMan(®) (Roche Diagnostics, Pleasanton, CA, USA). At the end of ivSIL treatment, 23/27 (85.1%) patients had undetectable HCV RNA. In one of the four remaining patients HCV RNA became undetectable 8 weeks after ivSIL on SOC. Five patients relapsed after ivSIL, three of them responded to repeated administration of ivSIL, but relapsed again. The best predictor of response was a low pre-ivSIL HCV RNA level. A total of 19 patients reached one treatment end point (end of SOC treatment HCV RNA undetectable n=11 and non-response n=8); 8 patients were still on SOC (all HCV-RNA-negative). All 11 patients with end-of-treatment response completed 24 weeks of follow-up; 7 patients remained HCV-RNA-negative and 4 relapsed. Except for a slight increase in bilirubin (mean ±SD 0.98 ±0.35 to 2.12 ±0.99 mg/dl), treatment was well-tolerated. ivSIL is an effective 'rescue treatment' for on-treatment non-responders to full-dose of SOC.

Efficacy of pegylated interferon plus ribavirin combination therapy for hepatitis C patients with normal ALT levels: a matched case–control study

The antiviral effect of pegylated interferon (Peg-IFN) plus ribavirin combination therapy in chronic hepatitis C (CHC) patients with normal alanine aminotransferase (ALT) levels (N-ALT) has been reported to be equivalent to that for patients with elevated ALT levels (E-ALT). However, the actual antiviral effect in N-ALT patients remains obscure because efficacy can be overestimated in patients with an advantageous background. In this study, 386 patients were extracted, for a matched case-control study, from 1320 CHC patients treated with Peg-IFN alpha-2b plus ribavirin combination therapy; 193 N-ALT patients [116 with hepatitis C virus genotype 1 (HCV-1), 77 with HCV genotype 2 (HCV-2)] were matched with 193 E-ALT patients by a propensity score method using the variables of age, sex, IFN treatment history, body mass index, and platelet counts. On multivariate analysis for sustained virological response (SVR) in N-ALT patients, younger age, low HCV RNA level at baseline, and HCV-2 were significant factors. The matched case-control study showed that the SVR rates of N-ALT patients were equivalent to those of E-ALT patients; at 49 and 40% in the HCV-1 group (P = 0.146), and 78 and 81% in the HCV-2 group (P = 0.691). However, in N-ALT patients with non-SVR, approximately 40% showed ALT elevation at 24 weeks post-treatment. Our findings indicate that the antiviral effect of Peg-IFN plus ribavirin therapy in N-ALT patients is comparable to that for E-ALT patients irrespective of their advantageous background; however, the application of this therapy for N-ALT patients, especially for those with HCV-1, should be considered carefully.

Identifying Hepatitis C Virus Genotype 2/3 Patients Who Can Receive A 16-Week Abbreviated Course of Peginterferon Alfa-2A (40Kd) Plus Ribavirin

The objective of this analysis was to compare sustained virological response (SVR) and relapse rates in patients with a rapid virological response (RVR, HCV RNA <50 IU/mL at week 4) randomized to 24 or 16 weeks of treatment with peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 800 mg/day in the multinational ACCELERATE study. The analysis was restricted to patients who received treatment for 80% or more of the planned duration. Of 1309 eligible patients, 863 individuals (65.9%) achieved an RVR and were included in this analysis (458 assigned to 16 weeks and 405 assigned to 24 weeks). The overall SVR rate was significantly higher in patients randomized to 24 weeks of treatment (91% versus 82%; P = 0.0006) and among patients infected with genotype 2 (92% versus 81%; P = 0.0010) but not genotype 3 (90% versus 84%; P = 0.1308). Relapse rates were significantly lower among all patients randomized to 24 weeks of treatment: overall (6% versus 15%, P < 0.0001); in those infected with genotype 2 (5% versus 17%, P = 0.0001), and genotype 3 (7% versus 14%, P = 0.0489). SVR rates in patients with a viral load of 400,000 IU/mL or less randomized to 24 and 16 weeks of treatment were similar, 95% and 91% (P = 0.2012). Significant pretreatment predictors of SVR included assignment to 24 weeks of treatment (P = 0.0006), absence of advanced fibrosis on liver biopsy (P = 0.0032), lower HCV RNA level (P = 0.0017), and lower body weight (P < 0.0001). The standard 24-week regimen of peginterferon alfa-2a (40KD) plus ribavirin is significantly more effective than an abbreviated 16-week regimen in genotype 2/3 patients who achieve an RVR. Abbreviated regimens may be considered in patients with a low baseline viral load who achieve an RVR.

Shortened treatment duration in treatment-naive genotype 1 HCV patients with rapid virological response: A meta-analysis

In hepatitis C virus genotype 1 (HCV-1) patients with a rapid viral decline within the first month of therapy, a 24-week course of pegylated interferon (PEG-IFN) alpha and ribavirin treatment has been claimed to be as efficient as the standard 48-week duration. We performed a meta-analysis of 7 randomized controlled trials comparing less than 48 weeks to 48 weeks PEG-IFN alpha/ribavirin treatment in 807 HCV-1 patients with rapid viral decline. SVR was significantly less frequent with short treatment duration than with 48 weeks of therapy, with a mean difference of -13.6% (95% CI: -22.8% to -4.4%, p=0.004). This difference was related to a higher relapse rate (mean difference: 9.9%, 95% CI: 4.1-15.7%, p<0.001). In a sensitivity analysis restricted to studies using only a weight-based ribavirin regimen, shorter therapy was also less efficient. In the subgroup of patients with undetectable HCV-RNA at week 4 and a low baseline HCV-RNA level (400,000 IU/ml), there was no significant difference in SVR rates between 24 and 48 weeks of treatment (mean difference: -3.10%, 95% CI: -8.6% to 2.4%, NS). In HCV-1 patients with a rapid virological response, 24 weeks of combination therapy with PEG-IFN alpha and ribavirin should be considered only in subjects with low baseline viral load. However, the optimal cut-off defining low baseline viral load and the impact of the presence of other factors capable of altering treatment response, remain subject to debate.

Clinical trial: randomized, double‐blind, placebo‐controlled study of nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C genotype 4

Nitazoxanide, licensed in the US for treatment of Cryptosporidium parvum and Giardia lamblia, inhibits hepatitis C virus replication in replicon systems. To evaluate the safety and efficacy of nitazoxanide monotherapy for the treatment of chronic hepatitis C. This multicentre, randomized, double-blind, placebo-controlled study randomized 50 adult patients with chronic hepatitis C genotype 4 at three centres in Egypt to nitazoxanide 500 mg tablet or placebo twice daily for 24 weeks. Patients were followed up every 4 weeks during treatment and for 24 weeks after therapy. Seven of 23 patients (30.4%) in the nitazoxanide group achieved undetectable serum HCV RNA compared to 0 of 24 in the placebo group during therapy (P = 0.004). Each of the seven responders had baseline HCV RNA levels < or =400 000 IU/mL. Six of the seven virological responders were followed up for 24 weeks after the end of treatment, and four patients (17.4% of 23 treated) had a sustained virological response. Adverse events were similar in the nitazoxanide and placebo groups. Nitazoxanide monotherapy is safe and effective in achieving sustained virological response in a modest number of patients with chronic hepatitis C genotype 4, particularly in patients with low baseline serum HCV RNA levels.

Role of Pegylated Interferon-α-2a and Ribavirin Concentrations in Sustained Viral Response in HCV/HIV-Coinfected Patients

The effect of simultaneous plasma concentrations of pegylated interferon-alpha-2a (pegIFN-alpha-2a) and ribavirin (Rbv) on viral response has not been addressed to date. Hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients received pegIFN-alpha-2a and Rbv under routine clinical care conditions. Plasma concentrations of the two drugs were measured using enzyme-linked immunosorbent assay and high-performance liquid chromatography after 2, 4, 8, and 12 weeks and at the end of the treatment period (24-48 weeks, according to HCV genotype and treatment duration). Large interindividual variability was observed in the plasma levels of both drugs. After multivariate analysis, only HCV genotype 3, low HCV-RNA levels, and pegIFN-alpha-2a exposure remained as independent factors associated with sustained viral response (SVR). The probability of attaining an SVR in HCV genotypes 1 and 4 was more than three to four times higher in patients with pegIFN-alpha-2a levels above the selected cutoff point. Early therapeutic drug monitoring of pegIFN-alpha-2a levels could be beneficial in improving current treatment outcomes.

Study on genetic polymorphism of DC-SIGNR and HCV virus load

目的 了解丙型肝炎患者DC-SIGN/DC-SIGNR基因颈区重复序列的遗传多态性分布,探讨DC-SIGNR基因多态性与丙型肝炎病毒(HCV)载量的关系.方法 采用PCR结合DNA测序对300例丙型肝炎患者DC-SIGNR重复序列多态性进行基因分型和测序分析;同时检测了患者的HCV病毒载量.结果 该研究发现携带7等位基因(中等的)的患者,其HCV病毒载量水平低于携带9等位基因(较长的)的患者(P＜0.05),此外7/7基因型的患者组其HCV病毒载量水平低于9/7基因型的患者组,两组的差异有统计学意义(P＜0.05),提示HCV病毒更易与携带较长DC-SINGR等位基因的患者结合.结论 DC-SIGNR遗传多态性可能与HCV病毒在个体内的复制有关。