Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for Prediction of Treatment Response in Patients with Chronic Hepatitis C.

Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of hepatitis C virus (HCV) infection. We investigated the clinical utility of the new HCV Ag assay for prediction of treatment response in HCV infection. We analyzed serum from 92 patients with HCV infection who had been treated with pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at baseline were significantly lower in patients with a sustained virologic response (SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA analysis (2.8 log10fmol/L vs. 3.27 log10fmol/L, P = 0.023). Monitoring of the viral kinetics by determination of HCV RNA and HCV Ag levels resulted in similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a 92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag assay may be used as a supplement for predicting treatment response in HCV infection, but not as an alternative to the HCV RNA assay.

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

BACKGROUND: To elucidate the benefits of successful antiviral therapy in chronic hepatitis C (CHC) patients METHODS: 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). RESULTS: 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). CONCLUSIONS: SVR resulted in significantly more favorable long-term outcomes, such as lower risk of progression to cirrhosis and HCC occurrence compared with non-SVR.

Serum cytokine levels in chronic hepatitis B patients receiving peginterferon alpha-2a therapy.

BACKGROUND: The relationship between cytokines and responses to peginterferon alpha-2a treatment in chronic hepatitis B patients has not yet been fully elucidated. We analyzed the serum levels of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, interferon-gamma, tumor necrosis factor-alpha, monocyte chemotactic protein-1 (MCP1) and epidermal growth factor during the treatment with peginterferon alpha-2a. METHODS: Ninety-three serum samples from 20 chronic hepatitis B patients were collected before, during and after 48 weeks of peginterferon therapy and were assayed for 12 cytokines. The patients were categorized as either virologic responders (VRs) or non-responders (NRs) according to their HBV DNA levels taken at 6th month during treatment. The Evidence Investigator (Randox, Antrim, UK), a protein chip analyzer, was used to quantify cytokines. RESULTS: Among the 12 cytokines, the levels of MCP1 were increased and the levels of IL-4 were decreased during the treatment in VRs. However these cytokines were not significantly changed in NRs in the treatment phases. Area under the receiver operating characteristic curve (AUROC) value of HBV DNA measured before the treatment was 0.81 in predicting VRs, and that of the baseline MCP1 was 0.76. IL-6 levels at 3rd and 6th months during the treatment also showed AUROC values 0.85 and 0.78 respectively in predicting sustained VRs. CONCLUSION: Serum cytokine levels reflect the pathological differences of individual treatment phases and could also be useful in monitoring responses to peginterferon treatment in chronic hepatitis B patients.

[A comparison of 24- vs. 48-week peginterferon plus ribavirin in patients with genotype 1 chronic hepatitis C].

BACKGROUND/AIMS: The standard therapy for patients with genotype 1 chronic hepatitis C (CHC) is a combination of peginterferon and ribavirin for 48 weeks. However, the most appropriate duration of treatment remains to be established because of treatment-related side effects and cost. The aim of this study was to compare the efficacies of 24- and 48-week treatments, and to assess the efficacy of split 24-week therapy (a further 24 weeks of treatment in patients with relapse after the initial 24 weeks of treatment). METHODS: A total of 130 patients with genotype 1 CHC was treated between June 2004 and December 2006. Patients with undetectable HCV RNA at 24 weeks of treatment (as assessed by qualitative PCR assay; n=101 patients) were allowed to choose either 24 or 48 weeks as the duration of their treatment; 51 patients chose the 24-week treatment regimen and the remainder chose the 48-week regimen. Patients who relapsed after 24 weeks of treatment were treated for further 24 weeks. The sustained virologic response (SVR) of each treatment group was analyzed. RESULTS: The SVR rate was higher in patients treated for 48 weeks than in those treated for 24 weeks (74.0% vs. 52.9%, P=0.028). In the multivariate analysis, age < 50 years, platelets > or = 150,000/mm(3), and treatment duration for 48 weeks remained significant independent predictors of SVR. Fourteen of the 24 patients who relapsed in the 24-week treatment group received split 24-week therapy, and 6 patients (42.9%) achieved SVR. The overall SVR rate did not differ significantly between the 24-week treatment group, including those who underwent 24-week split therapy (64.7%), and the 48-week treatment group (64.7% vs. 74%, P=0.311). CONCLUSIONS: The 24-week plus additional split 24-week therapy following failure is a useful treatment strategy for patients with genotype 1 CHC.

Predicting Liver-Related Events Using Transient Elastography in Chronic Hepatitis C Patients with Sustained Virological Response.

BACKGROUND/AIMS: Few studies have investigated prognostic factors for the development of liver-related events (LREs) in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). METHODS: We analyzed 190 patients with CHC who achieved SVR after treatment with pegylated interferon (peg-IFN) plus ribavirin. LREs were defined as any complications related to cirrhosis, hepatocellular carcinoma (HCC), or liver-related mortality. RESULTS: The mean age was 54.1 years, and 84 of the patients (44.2%) were male. The mean liver stiffness (LS) value at SVR was 7.1±5.4 kPa. During the follow-up period (median, 43.0 months), LREs occurred in 10 patients (5.3%; HCC in eight patients, ascites in one patient, and liver-related mortality in one patient). By multivariate Cox regression analysis, age, α-fetoprotein level, and LS value were independent predictors for LRE development (all p<0.05). Patients with LS values ≥7.0 kPa had a greater risk (hazard ratio, 9.472; 95% confidence interval, 1.018 to 88.126; p=0.048) for LRE development compared to those with LS values <7.0 kPa. CONCLUSIONS: The LS value at SVR is useful for predicting LRE development in CHC patients who achieve SVR after treatment with peg-IFN plus ribavirin. Thus, LRE surveillance strategies might be optimized according to the LS values at SVR, even with complete viral eradication.

An Observational, Multicenter, Cohort Study Evaluating the Antiviral Efficacy and Safety in Korean Patients With Chronic Hepatitis B Receiving Pegylated Interferon-alpha 2a (Pegasys): TRACES Study.

Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type.We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated.In HBeAg-positive patients, those who received PEG-IFN α-2a for 48 weeks showed significantly higher HBV DNA suppression (HBV DNA < 2000 IU/mL) than those who were treated for 24 weeks (48 weeks vs 24 weeks; at ET, 44.4% vs 36.7%, P = 0.035; at PT6, 35.9% vs 13.3%, P = 0.035). The HBeAg seroconversion rate at ET was 18.1% in 48-week treatment group, which is significantly higher than the 2.2% (P < 0.001) that was seen in 24-week treatment group. This finding also continued at PT6 (29.0% vs 10.0%, P < 0.001). Following 48 weeks of treatment in HBeAg-negative patients, HBV DNA suppression at ET was higher than in HBeAg-positive patients (87.8% vs 44.4%). AEs were typical of those associated with PEG-IFN α-2a.In naïve Korean HBeAg-positive CHB patients treated with PEG-IFN α-2a, higher rates of HBV DNA suppression and HBeAg seroconversion were achieved in the 48-week treatment group than in the 24-week treatment group without additional risk of AEs.