Posters – Sunday May 21, 2006  8:00AM  Hepatitis C

 

HCV Clinical Trials

Abstract S1057 – Stronger Baseline HCV-Specific Immunity Is Associated With A Higher Likelihood Of A Sustained Virological Response to Combination Antiviral Therapy Of Chronic Hepatitis C

J. R. Burton; J. Klarquist; K. Im; S. H. Belle; H. R. Rosen

 

Introduction:

Individuals who spontaneously clear HCV infection have vigorous HCV-specific cellular immune responses. African Americans (AA) have lower rates of spontaneous clearance and lower rates of response to antiviral therapy compared to Caucasians (CA). Aim: Investigate if pretreatment HCV-specific immune responses are related to race and whether they are associated with virologic outcome to combination therapy.

 

Methods:

Virahep-C is a multicenter NIH funded study of response to peginterferon and ribavirin for up to 48 weeks in 205 CA and 196 AA naďve, genotype 1 patients. Patients with detectable HCV RNA after 24 weeks of therapy were removed from treatment. The primary end-point was a sustained virological response (SVR) defined as undetectable HCV RNA at 24 weeks after completing therapy. CD4+ T cell responses quantified at baseline in 353 patients (174 CA and 179 AA) using sensative IFN-γ ELISpot (enzyme linked immunospot) assays. Briefly, 2.5x105 peripheral blood mononuclear cells (PBMC) were incubated with HCV core (aa 1-115), E2 (383-715), NS3 (1007-1534), NS4 (1569-1931), NS5 (2054-2995), CMV, negative control (SDS/SOD) and positive control (PHA/SEB) antigens for 40 hours. Univariate and multivariable regression analyses were performed to determine factors associated with SVR.

 

Results:

A combined, baseline HCV antigen response of ≥168 IFN-γ ELISpots/106 PBMC was significantly associated with SVR. 43.2% of patients at or above this threshold experienced SVR vs. 28.2% of those who did not (RR=1.53; p=0.007). Among CA, 53.3% at or above this threshold experienced SVR, as compared to 38.5% of CAs who did not. Among AA, 30.6% at or above this threshold experienced SVR, as compared to 22.5% who did not. Multivariable regression analysis confirmed the independent association of baseline IFN-γ ELISpot response with SVR (RR 1.37; p=0.04, see Table 1).

 

Conclusions:

Baseline HCV-specific immunity is associated with SVR in patients undergoing antiviral therapy irrespective of race. Further analyses of the factors associated with more vigorous CD4+ T cell responses to HCV that correlate with an SVR are needed.

 

This study is funded by the NIDDK through a cooperative agreement with partial support from Roche Laboratories Inc. through a CRADA with the NIH.

 

Variable

Relative Risk

95% CI

p-value

Total IFN-γ ELISpots ≥168 vs. <168 (per 106 PBMC)

1.37

1.01-1.85

0.042

Baseline viral level (log 10 IU/ml)

0.59

0.46-0.77

<0.0001

% max pegIFN dose taken in 1st 24 wks (per 10% inc)

1.38

1.18-1.64

<0.0001

CA vs. AA

1.74

1.29-2.37

0.0003

Ishak score

0.86

0.79-0.94

0.0006

Male vs. female

0.76

0.61-0.96

0.0226

 


Abstract S1058 – The impact of growth factors on Peg-Intron and Rebetol dose reduction in patients treated for genotype 1 chronic hepatitis C

M. Kugelmas; A. L. Sabel-Soteres; G. Spiegelman

 

Background:

·       When treating patients with chronic hepatitis C with pegylated interferon and ribavirin, hematologic toxicity is one of the most common reasons for dose reduction and discontinuation.  These dose reductions negatively affect the chance of achieving an early virologic response (EVR) during therapy in patients with genotype 1 chronic hepatitis C infection.

·       EVR, which is defined as ≥ log drop in HCV RNA from baseline at week 12 of treatment, is a recognized positive predictor of sustained virological respone (SVR). 

Aims

·       To determine whether the use of growth factors and more lenient platelet cutoff points during anti-HCV therapy results in better adherence to target doses of peginterferon alfa and ribavirin, hiher EVR rates, and higher SVR rate.

 

Methods:

Treatment-naive patients (N=160) with compensated chronic liver disease secondary to chronic hepatitis C due to genotype 1 HCV infection were randomly assigned to 2 treatment groups.

o      Patients who did not achieve a ≥ 2 log drop in HCV RNA from baseline by week 12 of treatment were excluded from the study and considered nonresponders

·       In Group A hemotologic abnormalities were managed by dose reductions

·       In Group B patients were managed with the use of group factors (below):

Hemotologic Abnormality

Management

Anemia (hemoglobin <12 g/dL or decreased >25% from baseline

  • In the event of anemia, patients received darbepoetin alfa 3 mg/kg subcutaneously (SQ) every two weeks
  • Patients must have documented adequate iron stores (normal serum iron, transferring saturation ≥ 20%, and ferritin ≥ 100 ng/mL) before starting darbepoetin alfa therapy

Neutropenia (absolute neutrophil count (ANC) <900/mm3

  • In the event of neutropenia, patients received filgrastim 300 ug SQ weekly
  • Filgrastim was administered at least 24 hours before all subsequent doses of peginterferon alfa-2b and was dosed to maintain an ANC ≥ 900/mm3 and < 10,000/mm3

Thrombocytopenia

  • The dose of peginterferon alfa-2b was reduced to 1.0 ug/kg/wk when platelet count dropped below 55,000/mm3
  • Peginterferon alfa-2b was discontinued if the platelet cound dropped below 30,000/mm3

 

Study End Points

·       Primary end point was assessment of end-of-treatment response at 48 weeks and SVR after 24 weeks of follow-up

·       Secondary end points

o      Biochemical response (ALT levels)

o      Safety

·       Interim data are presented for patients who completed at least 12 weeks of therapy.

Results

·       To date, 122 patients are enrolled in the study

o      Sixty-three patients (n=30 (group A); n=33 (group B) have completed at least 12 weeks of therapy

·       Patient demographics for the 63 interim-analysis patients are shown below:

o      Gender (42 males; 21 females)

o      Age, 46 ± 8 yo

o      Patients with high viral load (>800,000 IU/mL) 60.3%

o      Liver biopsy fibrosis score-mean 1.7

o      Weight—mean 80 kg, mean ± 15

o      Race:  Caucasian (n=55), African American (n=6), Hispanic (n=1)

Early Virologic Response Rates

·       In total, 23 (77%) of 30 patients in group A and 24 (73%) of 33 patients in group B achieved an EVR

Dose Reduction and Discontinuations

·       Overall, doses of anti-HCV treatments were significantly more likely to be reduced in group A than in group B (33 vs. 12%, respectively;  p=.04)

Group A

·       Ten (33%) of 30 patients in group A had dose reductions

·       Ribavirin dose was reduced in 5 patients (n=2 (anemia) and n=1 each (flu like symptoms, shortness of breath, and nondefined side effect))

·       Peginterferon alfa-2b dose was reduced in 9 patients (n=3 (low ANC); n=2 (thrombocytopenia); n=2 (flu-like symptoms); and n=2 (weight loss))

Group B

·       Dose reductions occurred in 4 (12%) of 33 patients in group B

o      Two patients required dose reduction (ribavirin for hemoglobin <10 g/dl and peginterferon alfa-2b for ANC <750/mm3)

o      Two patients had permanent dose reductions (ribavirin for nausea and peginterferon alfa-2b for weight loss)

·       Twenty-one (64%) of 33 patients in group B received growth factors (darbepoetin (n=16);  filgrastim (n=2); darbepoetin and filgrastim (n=3))

·       In both treatment groups, hemoglobin levels decreased from baseline through week 12

·       At week 12, hemoglobin levels were significantly lower in group A than in group B patients (11.1 g/dl vs 12.2 g/dl, respectively; p=.04

Conclusion

·       Use of growth factors prevents dose reductions of peginterferon alfa-2b and ribavirin in HCV genotype 1 patients receiving anti-HCV therapy

·       Use of growth factors maintains more physiologic hemoglobin levels

·       Ongoing results of this study will show whether use of growth factors allows for higher SVR rates.

Abstract S1063 – The usefulness of sPECAM-1 and sVCAM-1 serum concentrations measurement in the assessment of fibrosis, inflammatory activity and antiviral therapy effectiveness in chronic hepatitis C

K. Zwirska-Korczala; M. Kukla; A. Ziolkowski; A. Berdowska; E. Janczewska-Kazek; A. Gabriel; B. Rybus-Kalinowska; I. Korzonek-Szlacheta; T. Brzozowski; S. J. Konturek

 

Background:

Platelet/endothelial cell adhesion molecule-1 (PECAM-1) and vascular cell adhesion molecule (VCAM-1) soluble forms reflect their expression in the tissue. The study was undertaken to answer the question whether there exists a correlation of sPECAM-1 and sVCAM-1 serum levels with fibrosis stage and inflammatory activity and if their levels can predict antiviral therapy effectiveness.

 

Material and methods:

We studied 80 patients (40M/40F), aged 53.0±9.9 years, BMI 25.0±0.9 kg/m2 with chronic hepatitis C, receiving peginterferon and ribavirin. Control groups included 20 HCV Ab-positive patients with normal AST and ALT levels, without fibrosis and 14 healthy volunteers age and BMI matched. Scheuer’s scale was used for liver samples assessment. sPECAM-1 and sVCAM-1 measurements were made using commercial methods.

 

Results:

We observed higher sPECAM-1 serum concentration in the patients’ group compared to the control groups (p<0.001). They were lower in patients with inflammatory grade 1 than grade 2 or 3 (p=0.03), and in fibrosis stage 3 they were higher compared to stage 2 (p=0.01). After therapy sPECAM-1 level decreased (p<0.001) and was slightly but not significantly higher in non-responders. Serum sPECAM-1 levels correlated positively with inflammatory activity (r=0.35, p=0.02) and fibrosis stage (r=0.53, p<0.001). Serum sVCAM-1 levels were higher in patients than in the group of healthy volunteers (p<0.001). There was no correlation between serum sVCAM-1 concentrations and morphological features in the liver.

 

Conclusions:

sPECAM-1 serum levels may be fibrosis progression predictor. Further investigations are necessary to assess the relation between sPECAM-1 serum fluctuations and therapy effectiveness. Serum sVCAM-1 has limited diagnostic value in chronic hepatitis C.

 


Abstract S1059 – Results of a Phase II dose ranging study of orally administered celgosivir as monotherapy in chronic hepatitis C genotype-1 patients.

E. Yoshida; D. Kunimoto; S. S. Lee; M. Sherman; J. Heathcote; R. Enns

 

Background:

Celgosivir is a novel antiviral agent in clinical development for treatment of chronic hepatitis C virus (HCV) infection. Current standard therapy for HCV is associated with significant side effects and limited efficacy. Novel treatments for HCV infection must aim to provide improved efficacy and tolerability. Celgosivir and its active metabolite castanospermine are potent inhibitors of alpha-glucosidase I, a host enzyme that alters the processing of glycoproteins. Inhibition of this enzyme results in HCV envelope proteins that fail to fold correctly and inhibition of viral assembly and release. This dose ranging monotherapy study was designed to provide safety and efficacy data necessary to proceed to combination therapy studies.

 

Methods:

This Phase II study was a 12-week, randomized, dose-response, open-label, multi-center study in treatment-naďve or interferon-intolerant genotype-1 HCV infected patients. Patients were randomized to one of three celgosivir treatment groups:

(i)             200 mg qd (every day),

(ii)           400 mg qd, or

(iii)         200 mg bid (twice a day)

These doses were evaluated tolerability and serum HCV RNA during the study.

 

Results:

Forty-three patients were randomized (16-200 mg qd, 15-400 mg qd, 12-200 mg bid) with 35 (81%) patients completing 12 weeks of therapy.

 

There was no clinically relevant mean change in viral load from baseline when celgosivir was used as a monotherapy at the three dose levels test.

 

Two patients (5%)  had peak viral load reductions of ≥ 1 log10.  The first patient, randomized to the 200 mg bid group, peaked at Week 4 (-1 log10 drop) and subsequently dropped out due to non-compliance.  The second patient, randomized to the 200 mg qd group, had a peak reduction at Week 8 (-1 log 10 drop) and was found to be non-compliant past Week 10 through to study completeion.

 Mild to moderate gastrointestinal (GI) symptoms were the most frequently reported adverse events with 67% of patients reporting flatulence, 26% nausea and 49% diarrhea. Elevated serum creatine kinase (CK) levels were reported in all treatments groups (47% of patients) and appeared to be dose related with 12 (80%) patients in the 400 mg qd group compared with 5 (42%) patients at 200 mg bid and 3 (19%) patients in the 200 mg qd group. Elevations were asymptomatic, reversible and returned to baseline levels within weeks post-treatment. No serious adverse events were reported. Treatment was discontinued for adverse events in 4 patients.

 

Conclusion:

Celgosivir, used as monotherapy in chronic HCV infection, was well tolerated in all treatment groups with modest antiviral effect. GI symptoms, particularly mild to moderate diarrhea and flatulence, were the most frequently occurring adverse events. Elevated serum CK levels were noted in about half the patients but were reversible, not clinically significant, and returned to baseline levels post-treatment. Based on non-clinical synergy data, combination therapy of celgosivir with peginterferon alfa-2b with or without ribavirin may produce more significant antiviral activity and is the subject of an on-going study.   

 


Abstract S1060 – Comparison of Daily Consensus Interferon versus Peginterferon alfa 2a Extended Therapy of 72 Weeks for Peginterferon / Ribavirin Relapse Patients with Chronic Hepatitis C

S. Kaiser; H. Hass; B. Lutze; M. Gregor

 

Objective:

Treatment with pegylated interferon and RBV for 48 weeks in naive chronic Hepatitis C patients results in relapse rates of about 20 – 30 %.   Recently improved response rates have been observed in retreatment trials using an extended treatment duration of 72 weeks.

 

Methods:

The efficacy of CIFN daily dosing + RBV versus PEG IFN a2a + RBV for 72 weeks in patients with a prior relapse to 48 weeks of treatment with PEG IFN + RBV was evaluated. 81 patients have been included, with 83% having genotype 1. Average weight of patients was 78 kg. Patients were either treated with CIFN at 9 ug QD for 72 weeks or with PEG IFN a2a at 180 ug QW for 72 weeks, both in combination with weight-based RBV.

 

Results:

Data show that after the initial 12 weeks a primary response with undetectable serum HCV-RNA was observed in 83 % of patients in the CIFN QD group and in 78 % in the PEG IFN 180 ug group. At the end of treatment at week 72, a negative PCR was observed in 89 % in the CIFN group, and in 76% of the PEG IFN 180 ug group (diff. not significant). The sustained viral response rates (SVR) were 69 and 44 %, respectively (p<0.05), indicating a significantly higher relapse rate in patients treated with PEG IFN a2a.

 

No growth factors were used in this study. Three patients experienced grade III thrombocytopenias, while no grade IV neutropenias or thrombocytopenias were observed. The overall tolerability of the CIFN QD regimen was comparable to the PEG IFN a2a therapy, while the CIFN QD regimen lead to a higher rate of injection site reactions and a slightly higher drop out rate of 18% versus 12% for the PEG IFN a2a group. In contrast, hematologic grade III alterations were higher in the PEG IFN a2a group.

 

Conclusions:

Extended CIFN daily dosing combination therapy for 72 weeks shows promising response rates in comparison to PEG IFN a2a combination therapy in previous relapse patients to standard PEG IFN / RBV therapy. The data are especially interesting since most patients were genotype 1 relapsers. Although a significant proportion of patients experienced a second relapse after cessation of therapy, the overall sustained response rates are nevertheless promising showing a SVR in up to 70% of patients. It is concluded that extended treatment with CIFN in combination with RBV may be an effective treatment modality for this difficult-to-treat patient group.

 


Abstract S1061 – Higher Susceptibility of Peginterferon alfa 2a versus Peginterferon alfa 2b Nonresponder Patients with Chronic Hepatitis C to Retreatment with Consensus Interferon Daily Dosing and Ribavirin

S. Kaiser; H. Hass; B. Lutze; M. Gregor

 

Objective:

Current standard treatment with pegylated interferon (PEG IFN) and ribavirin (RBV) in genotype 1 patients shows sustained response rates of 31 – 47%, thus leaving more than half of the patients with a relapse or nonresponse to . Recently improved response rates have been observed in pilot trials using consensus interferon (CIFN) in combination therapy in PEG IFN / RBV nonresponders.

 

Methods:

The efficacy of CIFN daily dosing and induction therapy followed by CIFN / RBV in PEG IFN combination treatment nonresponders was evaluated. 95 patients have been included, with 9% having genotype 1. Average weight of patients was 76 kg. Patients were either treated with CIFN at 9 ug QD for 16 weeks or with CIFN 27 ug QD for 4 weeks, followed by 12 weeks of CIFN 18 ug QD. Thereafter, treatment was continued in all treatment groups with CIFN at 9 ug QD with weight-based RBV for 32 - 56 weeks, depending when a patient became first PCR negative, ensuring a treatment period for 48 weeks with a negative PCR.

 

Results:

Data show that after the initial 12 weeks of CIFN monotherapy, a primary response with undetectable serum HCV-RNA was observed in 35 % of patients with a prior nonresponse to PEG IFN a2b and in 51 % in prior PEG IFN a2a nonresponders. At the end of treatment, a negative PCR was observed in 37 % in PEG IFN a2b nonrespinders, and in 51% of PEG IFN a2a nonresponders. The sustained viral response rates (SVR) were 21% and 38% for PEG IFN a2b and PEG a2a nonresponders, respectively.

When response rates were calculated according to the treatment arm used, the SVR for PEG IFN a2b nonresponders were 18% in the CIFN 9 ug arm and 25% in the CIFN high dose arm. For PEG IFN a2a nonresponders the SVR were 34% and 41% for the CIFN 9 ug dose and high dose arms, respectively. The overall tolerability of the CIFN 9 ug regimen was comparable to a standard therapy with pegylated IFN and RBV, while the CIFN 27/18/9 ug regimen was less tolerable during the high dose induction period. However, drop out rates were not different between the two dosing regimen.

 

Conclusions:

CIFN daily dosing / induction therapy together with subsequent RBV combination therapy thus shows promising response rates in previous PEG IFN combination therapy non-responders. Especially PEG IFN a2a nonresponders appear to have a benefit from CIFN QD retreatment. It is concluded that CIFN may be an effective treatment modality for this difficult-to-treat patient group.

 


Abstract S1062 – Early viral response to CPG 10101, a new investigational antiviral TLR9 agonist, in combination with pegylated interferon and/or ribavirin, in prior relapse HCV responders: preliminary report of a randomized Phase 1 study

J. McHutchison; R. Ghalib; E. Lawitz; B. Freilich; P. Kwo; F. Masciari; J. L. Himes; M. Al-Adhami; B. Bacon

 

Background:

CPG 10101 (CPG) is an investigational Toll-like receptor 9 (TLR 9) agonist with antiviral activity. CPG directly activates B cells and plasmacytoid dendritic cells (pDC) and stimulates the innate immune system to produce Th1 cytokines, including those with known antiviral activity (e.g., IFN-α). This Th1 environment, combined with improved antigen presentation by pDC, promotes HCV-specific adaptive T cell responses. Standard treatment of chronic HCV with pegylated IFN-α (PEG) and ribavirin (RVN) for 24-48 weeks, results in sustained viral responses (SVR) in ~ 50% naďve genotype 1-infected patients. This study investigates CPG’s potential to exploit immune-mediated HCV infection control mechanisms when used with standard of care treatment in prior relapse patients.

 

Methodology:

Sevent-four  HCV genotype 1-infected adults that previously responded to ≥24 weeks PEG + RVN treatment, then relapsed with subsequent detection of HCV RNA within 6 months, are to be enrolled and randomized equally to five arms:

(i)             Peginterferon plus ribavirin

(ii)           CPG 10101 plus  Peginterferon plus ribavirin  

(iii)         CPG 10101 plus pegylated interferon  

(iv)         CPG 10101 plus ribavirin  

(v)           CPG 10101

Treatment is for 12 weeks:

CPG 101 =0.2 mg/kg SC weekly, Peginterferon =1.5 μg/kg SC weekly; ribavirin =800-1400 mg QD, po).

Hematology and chemistry are assessed at weeks 1, 2, 3, 4, 8 and 12 and HCV RNA (viral load assessed at baseline, weeks 2, 4, 8 and 12.

Summary of 12 week safety

·       CPG 10101 was generally well-tolerated

o      AE were transient and consistent with mechanism

·       No grade 2 anemia in any CPG-contain arm

·       No significant increase in severity of neutropenia following the addition of CPG 10101 to pegylated interferon with/without ribavirin

·       AEs were predominantly mild in intensity in all groups

o      Most frequent:  Pyrexia, fatigue, injection site reactions, headache, nausea

o      CPG 10101 mainly added mild AEs to Pegylated interferon and ribavirin

§       Predominantly injection site reaction

o      No withdrawals in CPG 10101 plus pegylated interferon plus ribavirin plus ribavirin arm

·       6 Withdrawals

o      2 drug-related AEs

·       Injection site cellulites & necrosis (CPG 10101 plus pegylated interferon) (serious AE)

·       Rash (CPG 10101)

·       2 lost to follow up

·       1 withdrew consent

·       1 non-compliance

o      1 additional CPG 10101-related serious adverse event at week 12

§       Immediate hypersensitivity (CPG 10101 plus pegylated interferon)

o      No evidence of ALT flares

Addition of CPG 10101 to pegylated interferon plus ribavirin increases HCV viral response, including HCV RNA undetectability at week 12.

Conclusions:

o      Actilon (CPG 10101) improves early antiviral activity of pegylated interferon plus ribavirin in previous relapsers to HCV therapy. 

o      Greater RVR, EVR, and HCV RNA undetectable (<50 IU/mL)

o      Additional HCV RNA undetectable responses in continuation period.

o      No viral breakthrough seen during continuation treatment of CPG 10101 plus pegylated interferon plus ribavirin

o      CPG 10101 appears synergistic with pegylated interferon and ribavirin

o      CPG 10101 is similar to pegylated interferon plus ribavirin EVR

o      CPG 10101 is generally well tolerated in combinations with pegylated interferon and/or ribavirin

o      Activity of CPG 10101 in humans is consistent with its activity in pre-clinical studies and with the known biology of TLR9

o      An additional randomized trial is underway in treatment-refractory non-responder patients

o      90 patients in 3 arm non-responder phase 2 trial

o      0.2 mg/kg CPG 10101 plus pegylated interferon plus ribavirin

o      0.5 mg/kg CPG 10101 plus pegylated interferon plus ribavirin

o      Pegylated interferon plus ribavirin

 


Abstract S1063 – The usefulness of sPECAM-1 and sVCAM-1 serum concentrations measurement in the assessment of fibrosis, inflammatory activity and antiviral therapy effectiveness in chronic hepatitis C

K. Zwirska-Korczala; M. Kukla; A. Ziolkowski; A. Berdowska; E. Janczewska-Kazek; A. Gabriel; B. Rybus-Kalinowska; I. Korzonek-Szlacheta; T. Brzozowski; S. J. Konturek

 

Background:

Platelet/endothelial cell adhesion molecule-1 (PECAM-1) and vascular cell adhesion molecule (VCAM-1) soluble forms reflect their expression in the tissue. The study was undertaken to answer the question whether there exists a correlation of sPECAM-1 and sVCAM-1 serum levels with fibrosis stage and inflammatory activity and if their levels can predict antiviral therapy effectiveness.

 

Material and methods:

We studied 80 patients (40M/40F), aged 53.0±9.9 years, BMI 25.0±0.9 kg/m2 with chronic hepatitis C, receiving peginterferon and ribavirin. Control groups included 20 HCV Ab-positive patients with normal AST and ALT levels, without fibrosis and 14 healthy volunteers age and BMI matched. Scheuer’s scale was used for liver samples assessment. sPECAM-1 and sVCAM-1 measurements were made using commercial methods.

 

Results:

We observed higher sPECAM-1 serum concentration in the patients’ group compared to the control groups (p<0.001). They were lower in patients with inflammatory grade 1 than grade 2 or 3 (p=0.03), and in fibrosis stage 3 they were higher compared to stage 2 (p=0.01). After therapy sPECAM-1 level decreased (p<0.001) and was slightly but not significantly higher in non-responders. Serum sPECAM-1 levels correlated positively with inflammatory activity (r=0.35, p=0.02) and fibrosis stage (r=0.53, p<0.001). Serum sVCAM-1 levels were higher in patients than in the group of healthy volunteers (p<0.001). There was no correlation between serum sVCAM-1 concentrations and morphological features in the liver.

 

Conclusions:

sPECAM-1 serum levels may be fibrosis progression predictor. Further investigations are necessary to assess the relation between sPECAM-1 serum fluctuations and therapy effectiveness. Serum sVCAM-1 has limited diagnostic value in chronic hepatitis C.